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HIV/HCV coinfection is associated with a rapid progression to liver damage. Specifically, NK cell population dysregulation is of particular interest, as these cells have been shown to block HCV replication effectively and have an anti-fibrogenic activity. The NKp30 receptor is linked to tumor cell lysis and has a crucial role during viral infections. In the present study, we determined the subpopulations of NK cells based on CD56 and CD16 expression, NKp30 receptor expression, its isoforms A, B, and C, along with the cytotoxicity molecules in patients with HIV/HCV. Results: evidenced by the APRI and FIB-4 indices, the HCV-infected patients presented greater liver damage than the HIV and HIV/HCV groups. The HCV group presented a decreased expression of NKp30 isoform A, and NK cell frequency was not different between groups; however, CD56brigth subpopulation, NKp30 receptor, and CD247 adaptor chain were decreased in HIV/HCV patients; further, we described increased levels of soluble IL-8, IL-10, IL-12, and IL-23 in the serum of HIV/HCV patients. Conclusions: HCV and HIV/HCV patients have multiple parameters of non-fitness status in NK cells; awareness of these dysfunctional immunological parameters in HIV/HCV and HCV patients can elucidate possible novel therapeutics directed towards the improvement of NK cell fitness status, in order to improve their function against liver damage. [Display omitted] • HCV-infected patients presented greater liver damage. • CD56brigth NK cells, NKp30, and CD247 were diminished in HIV/HCV patients. • A decreased mRNA expression of NKp30 isoform A was seen in HCV patients. • Increased levels of soluble IL-8, IL-10, IL-12, and IL-23 were found in HIV/HCV patients. • Liver damage and NKp30+CD247+ NK cell frequency had a negative correlation. [ABSTRACT FROM AUTHOR]

Chronic or excessive use of realgar induced liver damage. The biomarkers and exact mechanism have not been fully investigated. We performed an untargeted lipidomics study to investigate the effects of realgar on liver lipidome in mice and explore the sensitive biomarker model of realgar induced liver damage. It was found that realgar exposure induced arsenic accumulation in the liver, increased ROS generation, elevated MDA levels, decreased antioxidant enzymes levels, induced cell apoptosis, changed hepatocyte ultrastructure and morphology, and altered ALT, AST levels. Lipidomics study detected 30 classes and 1457 molecules in mice liver. The numbers of 49 and 103 lipid molecules were significantly altered (FDR <0.05) in the livers of 0.45 g/kg and 1.35 g/kg realgar-exposed mice. The glycerophospholipid and sphingomyelin were the most affected lipid class. We focused on the effect of chronic realgar exposure on the mutual transformation of lipid subclasses and the fatty acid chain composition of lipids in mouse liver, and found that realgar affected the mutual transformation of PE-PC, PC-LPC and SM-Cer. Notably, we found that realgar exposure increased PUFAs linked phospholipids in mouse liver tissues. We identified two sensitive lipid molecules [PE (44:2p) and PE (16:0/22:5)] in combination can accurately distinguish and predict realgar induced liver damage, they are associated with oxidative damage and mitochondrial respiration in liver tissue. Our study provides an experimental basis for the mechanism research and early detection of realgar-induced liver damage. [Display omitted] • Chronic realgar exposure disturbed lipid metabolism in the mouse liver revealed by lipidomics. • 1457 lipids were identified, and glycerophospholipid and sphingomyelin were the most affected. • Chronic realgar exposure changed the mutual transformation of lipid classes. • Chronic realgar exposure increased PUFAs linked phospholipids in mouse liver tissues. • A sensitive lipid biomarker model involving two lipid molecules were developed. [ABSTRACT FROM AUTHOR]

As a potent stressor, environmental cold stress induces severe mitochondrial dysfunction with the overproduction of reactive oxygen species (ROS) in fish, resulting in liver damage. However, the molecular mechanisms underlying the cold-induced liver damage remain unclear. In the present study, the cold-inducible RNA-binding protein (CIRBP) from Takifugu fasciatus was characterized, and its role in cold-induced oxidative stress damage was investigated. An acute liver injury model was constructed by exposing T. fasciatus individuals to temperatures of 25, 19, and 13 °C. Cold exposure markedly induced histomorphological liver injury and triggered endogenous apoptosis and NLRP3 inflammatory response. Cold treatment significantly increased CIRBP gene expression. A similar expression pattern was detected for thioredoxin (TRX), suggesting that these two proteins play a role in the establishment of cold adaptation. CIRBP binds directly to the 3′-UTR of TRX. Furthermore, in vivo experiment showed that, when CIRBP expression in T. fasciatus is knocked down, the time to loss equilibrium significantly shortened at 13 °C. Taken together, our study revealed that CIRBP is a critical protective factor against cold induced liver damage and that the CIRBP/TRX pathway could function as an underlying mechanism for cold adaptation in teleosts. • Cold exposure significantly increased CIRBP expression in Takifugu fasciatus. • Cold treatment induced liver histomorpholotical injury, apoptosis and inflammatory response. • CIRBP attenuates cold-induced hepatotoxicity through TRX system. • CIRBP binds to 3′ UTR of TRX mRNA to maintain intracellular homeostasis under cold stress. [ABSTRACT FROM AUTHOR]

Animal models, mainly murine, stay as a fundamental resource in diverse research pursuits, notably contributing to significant strides in discovering novel treatments for therapeutic applications. Preclinical assays must consider the existence of self-recovery mechanisms in the murine species to achieve a well-designed control group. This study focuses on unveiling the innate rapid regenerative capacity of rat liver by utilizing the thioacetamide-induced sub-chronic liver injury model. Employing histopathological, biochemical, and molecular liver function tests, we assessed the recovery of liver tissue functionality. Moreover, animals were housed with voluntary running wheels and locomotory activity was recorded and employed as an indirect index of overall animal recuperation. Remarkably, basal locomotory activity reestablished to normal levels only two weeks post-thioacetamide exposure. Our results raise vital considerations about the importance of temporal synchronicity in comparative assays to validate the real action of treatments, emphasizing the role of the rapid rat liver endogenous self-recovery. [Display omitted] [ABSTRACT FROM AUTHOR]

The prevalence of non-alcoholic fatty liver disease (NAFLD) has increased concomitantly with heightened exposure to environmental chemicals, such as benzophenone-type ultraviolet (BP-type UV) filters and parabens, which are prevalent in personal care products. This study aimed to investigate the potential link between the exposure to these chemicals and the risk of developing NAFLD. We conducted a case-control study involving 228 participants from South China, encompassing individuals diagnosed with NAFLD and healthy controls. Blood samples were collected and analyzed for the presence of 11 parabens and 8 BP-type UV filters. The findings revealed significantly elevated concentrations of several parabens and BP-type UV filters in the blood of patients with NAFLD compared with the healthy cohort. Notably, methylparaben (MeP), ethylparaben (EtP), isopropylparaben (iPrP), butylparaben (BuP), isobutylparaben (iBuP), 3,4-dihydroxybenzoic acid (3,4-DHB), total parabens (Σparabens), BP1, BP3, BP4, and 4-hydroxybenzophenone (4-OH-BP) were identified as significant predictors of NAFLD prevalence. Through multiple regression analyses, the blood levels of iBuP, Σparabens, and BP4 were found to be significantly associated with elevated triglycerides (TG) (β = 0.59 mmol/L, 95% CI = 0.11–1.59), total bilirubin (TBIL) (β = 2.81 μmol/L, 95% CI = 0.46–15.6) or direct bilirubin (DBIL) (β = 1.89 μmol/L, 95% CI = 0.47–10.2), and reduced globulins (GLB) (β = −0.29 g/L, 95% CI = −0.07 to −5.45), respectively, which are indicators of liver damage. Moreover, TBIL and DBIL were found to mediate 26.7% and 24.6% of the increase in NAFLD prevalence associated with Σparabens, respectively. In conclusion, this study offers pioneering insights into human exposure to parabens and BP-type UV filters as well as their hepatotoxic potential. [Display omitted] • Parabens and BP-UV filters linked to higher NAFLD risk. • Exposure levels significantly higher in NAFLD patients. • IBuP, Σparabens, BP4 associated with liver damage markers. • Potential mediation of NAFLD risk via bilirubin metabolism. [ABSTRACT FROM AUTHOR]

[Display omitted] • WK alleviated liver damage induced by SPF in OVX rats. • The metabolism disorder induced by SPF was reversed after being treated with WK in a compatible manner. • The protective effect of WK on SPF-induced liver damage was associated with the regulation of bile acid metabolism. Walnut kernel (WK) is a globally popular health food known for its potent antioxidant properties. WK shows a promising prospect in protecting against liver damage induced by salt processed psoraleae fructus (SPF). This study explored the impact of WK in mitigating liver damage induced by SPF in an ovariectomized (OVX) rat model. Serum metabolomics was employed to explore potential detoxification mechanisms. The levels of Farnesoid X receptor (FXR), Bile salt export pump (BSEP), and Cholesterol 7α-hydroxylase (CYP7A1) proteins were determined through western blot analysis. The results demonstrated that WK exhibits a noteworthy protective effect against liver damage induced by SPF. The WK normalized the metabolic disorder and reversed sixteen liver injury biomarkers and five metabolic pathways induced by SPF. These results demonstrated that WK exhibits a protective effect against SPF-induced liver damage in OVX rats by regulating bile acid metabolism. [ABSTRACT FROM AUTHOR]

In Guangzhou and Guangxi, China, Abrus cantoniensis Hance (AH) is known for its liver-protective properties and is commonly used in herbal teas and soups. In the herbal market and pharmaceutical preparations, AH and Abrus mollis Hance (AMH) are often used interchangeable. Despite their morphological and usage similarities, distinguishing their differences is essential for scientific research and clinical practice. This study focuses on the morphological identification, chemical composition, and hepatoprotective effectiveness of AH and AMH. It aims to evaluate their interchangeable use and provide a rationale for this practice. This research helps regulate the market of AH medicinal materials, ensuring clinical safety and effectiveness. Samples of AH and AMH roots, stems, leaves, and seeds were collected and photographed using a stereoscope and digital imaging system. The chemical components of AH and AMH were qualitatively analyzed using UPLC-Q/TOF-MS. Chemometric techniques, such as PCA and OPLS-DA, were employed to discern the componential differences between the two species. A CCl 4 -induced acute liver injury mouse model was developed to assess hepatoprotective effects. The hepatoprotective properties of AH and AMH were evaluated by analyzing the liver index, H&E staining, changes in serum liver function indicators (TBIL, ALT, AST), and concentrations of SOD, MDA in liver homogenate. The root color, texture, stem diameter, cross-sectional characteristics, leaf shape, and seed morphology of the two plants were observed. Notable differences were identified, which can be used for accurate identification. The UPLC-Q/TOF-MS identified 50 compounds in both species, which were classified into 3 alkaloids, 22 flavonoids, 2 triterpenes, 10 triterpene saponins, 10 amides, and 3 others, and 20 different compounds between AH and AMH were screened by chemometrics. By improving serum biomarkers (ALT, AST, TBIL) and regulating oxidative stress markers (SOD, MDA), the alleviating effect of AH and AMH extracts on liver injury was confirmed. Notably, AH showed a stronger liver protective effect, significantly reducing ALT and AST levels more than AMH. This study enhances understanding of the morphological identification, chemical profiling, and hepatoprotective effects of AH and AMH. It provides a reference for future scientific research and the clinical application of AH in treating liver damage. [Display omitted] [ABSTRACT FROM AUTHOR]

Paraquat (PQ) is among the most widely used herbicides in the agriculture sector worldwide and is extremely noxious to both animals and humans. Paraquat exposure damages various organs in the body, particularly the liver. Sciadopitysin (SCD), a biflavonoid that is reported in Ginko biloba leaves, shows diverse biological potentials such as antioxidant and anti-inflammatory effects. The primary focus of this research was to estimate the effects of SCD against PQ-instigated hepatic toxicity in rats. Forty-eight male albino rats were randomly split into 4 groups: control group, PQ (5 mgkg−1) treated group, PQ (5 mgkg−1) + SCD (2 mgkg−1) co-treated group and SCD (2 mgkg−1) only treated group. After 30 days of experimentation, PQ exposure lowered the expression of Nrf-2 and antioxidants genes, while increasing the expression of Keap-1. The activities of antioxidants, including heme oxygenase-1 (HO-1), catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GSR), glutathione peroxidase (GPx), and glutathione (GSH) as well as total protein levels, were reduced following PQ administration. Moreover, malondialdehyde (MDA) and reactive oxygen species (ROS) contents were elevated in PQ exposed rats. PQ intoxication also increased the expressions of Bax and Caspase-3, while down-regulating Bcl-2 expressions. Furthermore, PQ exposure induced morphological alterations in the liver. Nevertheless, SCD treatment reduced all PQ-elicited damages in the liver of rats owing to its free radical scavenging potential. [ABSTRACT FROM AUTHOR]

The liver is a vital organ in human physiology positioned in the upper right quadrant of the peritoneal cavity, which plats a critical role in metabolic processes, detoxification of various substances and overall homeostasis. Along with these critical functions, hepatic diseases impose as significant global health threat. Liver illness is the cause of two million fatalities every year, or 4% of all deaths. Traditionally, healthcare providers have prescribed antibacterial and antiviral medications to address liver illness. Nephrotoxicity is a frequently observed negative reaction to drugs, with the majority of such events happening in individuals who have advanced cirrhosis. Thus, recognizing this gap, there is a dire need of exploration of pharmaceutical alterative for hepatic diseases, with special focus on their efficacy and reduced toxicity. Fruits have long been known to therapeutic impact on human health, thus exploration of fruits components namely pulp, seeds and peels containing phytochemicals have emerged as a promising avenue for hepatoprotective interventions. Thus, review comprehends the information about worldwide burden of chemical induced toxicity and injuries as well as highlight the on-going challenges in hepatic disease management. It also shed light on the valuable contributions fruit parts and their phytocompounds obtained from different components of fruits. Fruit pulp, especially when rich in flavonoids, has demonstrated significant potential in animal model studies. It has been observed to enhance the activity of antioxidant enzymes and reduce the expression of pro-inflammatory markers. The methanolic and ethanolic extracts have demonstrated the most favorable outcomes. Further, this review also discusses about the safety assessments of fruits extracts for their utilization as hepatoprotective agents. [Display omitted] • CCl 4 and paracetamol causes hepatotoxicity due to lipid peroxidation, alkylation and reactive intermediate, NPAQI. • Alcohol causes the hepatotoxicity due to hepatic lesions, increases proinflammatory mediator levels. • These chemical stresses are associated with liver fibrosis, cirrhosis, and fatty liver. • Pulp is among the most studied fruit part in the treatment of liver disorders. • Stilbenoids and flavonols are the mostly studied polyphenols in the treatment of liver toxicity. [ABSTRACT FROM AUTHOR]

Benzo[ a ]pyrene (BaP) as a carcinogen induces oxidative stress and inflammation, causing health problems including liver damage. Puerarin (a natural flavonoid) is traditionally used to provide hepatoprotective effects. This research was established to meet the rising demand for effective therapies/treatments against hepatic diseases and investigate the mechanism underlying the protective actions of puerarin against BaP-induced liver damage. In mice, puerarin combated effectively the detrimental changes in liver weight, color and function indices caused by BaP. In HepG2 cells, puerarin alleviated BaP-induced cell death, oxidative stress and inflammation, and such effects were positively correlated with puerarin's concentration (12.5–50 μM). Mechanistic studies revealed that BaP induced low Sirt1 expression and high miR-34a-5p expression, and puerarin treatment alleviated these changes. Oxidative stress and inflammation induced by BaP were almost eliminated when miR-34a-5p was silenced. Inhibiting miR-34a-5p or overexpressing Sirt1 had a similar effect to puerain treatment. Overexpression of miR-34a-5p and inhibition of Sirt1 reduced the protective effect of puerarin. Collectively, miR-34a-5p participates in the regulation of puerarin's protective function against BaP-induced injury through targeting Sirt1. There is a novel pathway for suppressing oxidative stress and inflammation via miR-34a-5p/Sirt1 axis in puerarin-mediated hepatoprotection, which opens up a new avenue for alternative therapies. [Display omitted] • BaP causes liver damage via inducing oxidative stress and inflammation in mice and HepG2 cells. • Puerarin plays a hepatoprotective role against BaP-induced damage. • MiR-34a-5p/Sirt1 axis involves in the protection of puerarin against BaP-induced hepatotoxicity. [ABSTRACT FROM AUTHOR]

To investigate the utility of T1ρ and T2 relaxations for assessing the severity of liver fibrosis (F stage) and necro-inflammation (A stage) in patients with chronic liver disease (CLD). We calculated T1ρ and T2 relaxations of the liver parenchyma in 82 patients who underwent liver surgery. F and A stages of enrolled patients were assessed by referring to surgically resected specimens. The relationships between T1ρ or T2 relaxation and F or A stage were assessed using one-way analysis of variance followed by Tukey's multiple comparison test, Spearman's rank correlation test and a receiver operating characteristic analysis. The T1ρ and T2 values of the liver parenchyma were significantly increased as the F and A stages progressed. The T1ρ and T2 values showed significant differences between F0 and F4, between F1 and F4, and between F2 and F4. In addition, T1ρ values showed a significant difference between F0 and F3 as well. The highest diagnostic ability for fibrosis was obtained when differentiating ≥F3 from ≤F2 using T1ρ: the sensitivity was 82.8%, the specificity 79.2% and the area under the curve (AUC) 0.87. The sensitivity and AUC of T1ρ relaxation (46.9% and 0.67) were significantly higher than those of T2 relaxation (29.7% and 0.60) for differentiating ≥A1 from A0. T1ρ and T2 relaxations have potential as a biochemical marker for assessing the severity of liver fibrosis and necro-inflammation. T1ρ relaxation may be slightly superior to T2 relaxation in terms of diagnostic ability for liver fibrosis and necro-inflammation. [ABSTRACT FROM AUTHOR]

[Display omitted] • PFOA cause liver damage and influence urea synthesis. • PFOA has effects on sera biochemical parameters, which are ALT, GGT, BILD and UREA. • iTRAQ-based quantitative proteomics analysis revealed 112 significantly upregulated proteins and 80 downregulated proteins. • 8 proteins were associated with fatty acid oxidation and 2 proteins were associated with urea cycle. Perfluorooctanoic acid (PFOA) is a typical C8 representative compound of perfluoroalkyl and polyfluoroalkyl substances (PFAS) widely used in industrial and domestic products. It is a persistent organic pollutant found in the environment as well as in the tissues of humans and wildlife. Despite emerging scientific and public interest, the precise mechanisms of PFOA toxicity remain unclear. In this study, male rats were exposed to 1.25, 5, and 20 mg PFOA/kg body weight/day for 14 days by gavage; food intake and bodyweight changes were recorded every day. After 14 days, blood was collected for sera biochemistry, livers were quickly stripped and weighed after execution. Part of the liver tissue was frozen by liquid nitrogen for iTRAQ-Based Quantitative Proteomics Analysis; and some was fixed in 4% paraformaldehyde (PFA) for histological section and hematoxylin-eosin (HE) staining. Urine samples were also collected and monitored by raising rats in metabolic cages. Real-time quantitative PCR and western blot was used to validate the proteomics assay after bioinformatics analysis. The results demonstrate that 20 mg/kg/d PFOA exposure cause body weight loss and significant liver swelling and reduced urea metabolism. The sera biochemistry assay shows that ALT, GGT, BILD and UREA levels have significant changes compared with normal control group and reference range of rat sera. The subsequent iTRAQ-based quantitative proteomics analysis of rat livers identified 3,327 non-redundant proteins of which 112 proteins were significantly upregulated and 80 proteins were downregulated. Gene ontology analysis revealed proteins are primarily involved in cellular, metabolic and single−organism processes. Among them, eight proteins (ACOX1, ACOX2, ACOX3, ACSL1, EHHADH, GOT2, MTOR and ACAA1) were related to oxidation of fatty acids and two proteins (ASS1 and CPS1) were found to be associated with urea cycle disorder. The downregulation of urea synthesis proteins ASS1 and CPS1 after exposure to PFOA was then confirmed through qPCR and western blot analysis. Together, these data demonstrate that PFOA exposure directly influences urea metabolism and provides insight into specific mechanisms of hepatotoxicity as a result of PFOA exposure. [ABSTRACT FROM AUTHOR]

[Display omitted] • Spred2-/- mice developed exacerbated Con A-induced liver damage with increased IFNγ production. • MEK/ERK inhibitor U0126 markedly inhibited the damage and reduced IFNγ production. • Neutralization of IFNγ abolished the damage with down-regulated hepatic STAT1 activation. • Depletion of CD4+/CD8+ T cells improved the damage with decreased IFNγ production. • Transplantation of CD4+/CD8+ T cells into RAG1-/- mice reproduced severe liver damage. • Liver damage and IFNγ production were significantly lower in Spred2 transgenic mice. Mitogen-activated protein kinases (MAPKs) are involved in T cell-mediated liver damage. However, the inhibitory mechanism(s) that controls T cell-mediated liver damage remains unknown. We investigated whether Spred2 (Sprouty-related, EVH1 domain-containing protein 2) that negatively regulates ERK-MAPK pathway has a biological impact on T cell-mediated liver damage by using a murine model. We induced hepatotoxicity in genetically engineered mice by intravenously injecting Concanavalin A (Con A) and analyzed the mechanisms using serum chemistry, histology, ELISA, qRT-PCR, Western blotting and flow cytometry. Spred2-deficient mice (Spred2-/-) developed more sever liver damage than wild-type (WT) mice with increased interferon-γ (IFNγ) production. Hepatic ERK phosphorylation was enhanced in Spred2-/- mice, and pretreatment of Spred2-/- mice with the MAPK/ERK inhibitor U0126 markedly inhibited the liver damage and reduced IFNγ production. Neutralization of IFNγ abolished the damage with decreased hepatic Stat1 activation in Spred2-/- mice. IFNγ was mainly produced from CD4+ and CD8+ T cells, and their depletion decreased liver damage and IFNγ production. Transplantation of CD4+ and/or CD8+ T cells from Spred2-/- mice into RAG1-/- mice deficient in both T and B cells caused more severe liver damage than those from WT mice. Hepatic expression of T cell attractants, CXCL9 and CXCL10, was augmented in Spred2-/- mice as compared to WT mice. Conversely, liver damage, IFNγ production and the recruitment of CD4+ and CD8+ T cells in livers after Con A challenge were lower in Spred2 transgenic mice, and Spred2-overexpressing CD4+ and CD8+ T cells produced lower levels of IFNγ than WT cells upon stimulation with Con A in vitro. We demonstrated, for the first time, that Spred2 functions as an endogenous regulator of T cell IFNγ production and Spred2-mediated inhibition of ERK-MAPK pathway may be an effective remedy for T cell-dependent liver damage. [ABSTRACT FROM AUTHOR]

Aflatoxins (AFs) are a class of mycotoxins produced by the toxigenic Aspergillus fungi and are common contaminants of foods and feeds. Aflatoxin B1 (AFB1), the most potent aflatoxin, is well characterized to reduce productive performance and mortality in broilers. This exclusive review summarizes the efficacy of various plant products and phytochemicals to counteract AFB1 toxicity in broilers. The biochemical and molecular mode of action of AFB1 to induce liver damage, genotoxicity, immunosuppression and the protective effect of plant products against such mechanisms and their toxic effects are discussed. The link between antioxidant, immunomodulatory and hepatoprotective functions of plant products; oxidative stress and AFB1 macromolecular adducts mediated AFB1 toxicity are covered. Efficacy of Satureja khuzistanica, Zataria multiflora Boiss, Thymus vulgaris, Sauropsus androgynus , Hemidesmus indicus , Leucas aspera , Moringa oleifera , Eclipta alba , Curcuma longa, Silybum marianum, Urtica dioica , and citrus fruit are summarized. The anti-aflatoxic effect of water-soluble substances of wheat, grape seed proanthocyanidin extract and phytochemicals like thymol, carvarol, piperine, transcinnamaldehyde, resveratrol, curcumin, and silymarin are also discussed. Specific plant products and phytochemicals are shown to be effective against AF toxicity in broilers and could represent an important tool to reduce health and economic losses associated with AFB1 exposure. [Display omitted] • Aflatoxin contamination of feeds is a key issue in poultry production. • Oxidative stress, inflammation, liver damage and immunotoxicity are the major mechanisms of AF induced toxicity in broilers. • Plant products modulate AFB1 activation and AFB1 induced hepatic oxidative stress, inflammation and apoptosis in broilers. • Efficacious phytoproducts reduce aflatoxin toxicity in broilers by targeting their toxicity mechanisms. [ABSTRACT FROM AUTHOR]

Ebola virus (EBOV), a major global health concern, causes severe, often fatal EBOV disease (EVD) in humans. Host genetic variation plays a critical role, yet the identity of host susceptibility loci in mammals remains unknown. Using genetic reference populations, we generate an F2 mapping cohort to identify host susceptibility loci that regulate EVD. While disease-resistant mice display minimal pathogenesis, susceptible mice display severe liver pathology consistent with EVD-like disease and transcriptional signatures associated with inflammatory and liver metabolic processes. A significant quantitative trait locus (QTL) for virus RNA load in blood is identified in chromosome (chr)8, and a severe clinical disease and mortality QTL is mapped to chr7, which includes the Trim5 locus. Using knockout mice, we validate the Trim5 locus as one potential driver of liver failure and mortality after infection. The identification of susceptibility loci provides insight into molecular genetic mechanisms regulating EVD progression and severity, potentially informing therapeutics and vaccination strategies. [Display omitted] • CC genetic reference population identifies genetic loci regulating EBOV pathogenesis in mice • An F2 population from two CC lines is either highly resistant or vulnerable to EBOV infection • A major locus on chromosome 7, encoding Trim5 , drives severe EVD-like disease in mice • Gene expression signatures of liver damage mirror severe EVD in humans Schäfer et al. use a genetic screening platform based on the collaborative cross (CC) to identify and elucidate the role of the Trim5 locus during Ebola virus (EBOV) infection and the development of EBOV disease (EVD) in mice. [ABSTRACT FROM AUTHOR]

While N, N' -substituted p -phenylenediamines (PPDs) and their quinone derivatives (PPDQs) have been widely detected in the environment, there is currently limited data on their occurrence in humans. In this study, we conducted the first serum analysis of two PPDs and PPDQs in the healthy and secondary nonalcoholic fatty liver disease (S-NAFLD) cohorts in South China. The concentrations of four oxidative stress biomarkers (OSBs), namely, 8- iso -prostaglandin F 2α (8-PGF 2α), 11 β -prostaglandin F 2α (11-PGF 2α), 15(R)-prostaglandin F 2α (15-PGF 2α), and 8-hydroxy-2'-deoxyguanosine in serum samples were also measured. Results showed that N -(1,3-dimethybutyl)- N' -phenyl- p -phenylenediamine (6PPD) quinone was the predominant target analytes both in the healthy and S-NAFLD cohorts, with the median concentrations of 0.13 and 0.20 ng/mL, respectively. Significant (p < 0.05) and positive correlations were found between 6PPD concentration and 8-PGF 2α , 11-PGF 2α , and 15-PGF 2α in both the healthy and S-NAFLD cohorts, indicating that 6PPD may be associated with lipid oxidative damage. In addition, concentrations of 6PPD in serum were associated significantly linked with total bilirubin (β = 0.180 μ mol/L, 95%CI: 0.036–0.396) and direct bilirubin (DBIL, β = 0.321 μ mol/L, 95%CI: 0.035–0.677) related to hepatotoxicity. Furthermore, 8-PGF 2α , 11-PGF 2α , and 15-PGF 2α mediated 17.1%, 24.5%, and 16.6% of 6PPD-associated DBIL elevations, respectively. Conclusively, this study provides novel insights into human exposure to and hepatotoxicity assessment of PPDs and PPDQs. [Display omitted] • First study to report serum levels of PPs in humans. • Associations between the levels of 6PPD and lipid oxidative stress biomarkers were found. • Exposure to 6PPD may increase the odds of prevalent S-NAFLD in the South China cohort. • 6PPD exposure was associated with increased levels of TBIL and DBIL in humans. • Lipid peroxidation mediated the impact of PPs exposure on liver damage. [ABSTRACT FROM AUTHOR]

Although selenium (Se) and cadmium (Cd) often coexist naturally in the soil of China, the health risks to local residents consuming Se-Cd co-enriched foods are unknown. In the present study, we investigated the effects of chemical-based selenocystine (SeCys 2) on cadmium chloride-induced human hepatocarcinoma (HepG2) cell injury and plant (Cardamine hupingshanensis)-derived SeCys 2 against Cd-induced liver injury in mice. We found that chemical- and plant-based SeCys 2 showed protective effects against Cd-induced HepG2 cell injury and liver damage in mice, respectively. Compared with Cd intervention group, co-treatment with chemical- or plant-based SeCys 2 both alleviated liver toxicity and ferroptosis by decreasing ferrous iron, acyl-CoA synthetase long-chain (ACSL) family member 4, lysophosphatidylcholine acyltransferase 3, reactive oxygen species and lipid peroxide levels, and increasing ACSL3, peroxisome proliferator-activated receptor α, solute carrier family 7 member 11 (SLC7A11) and glutathione and glutathione peroxidase 4 (GPX4) levels. In conclusion, chemical- and plant-based SeCys 2 alleviated Cd-induced hepatotoxicity and ferroptosis by regulating SLC7A11/GPX4 signaling and lipid peroxidation. Our findings indicate that potential Cd toxicity from consuming foods grown in Se- and Cd-rich soils should be re-evaluated. This study offers a new perspective for the development of SeCys 2 -enriched agricultural products. [Display omitted] • Chemical-based SeCys 2 reduced Cd-induced HepG2 cell toxicity. • Plant-derived SeCys 2 alleviated Cd-induced liver damage in mice. • SeCys 2 inhibited ferroptosis by regulating SLC7A11/GPX4 signals. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances (PFAS) are a large group of stable synthetic surfactants that are incorporated into numerous products for their water and oil resistance and have been associated with adverse health effects. The present study evaluated the systemic and immunotoxicity of sub-chronic 28- or 10-day dermal exposure of PFHxS (0.625–5% or 15.63–125 mg/kg/dose) in a murine model. Elevated levels of PFHxS were detected in the serum and urine, suggesting that absorption is occurring through the dermal route. Liver weight (% body) significantly increased and spleen weight (% body) significantly decreased with PFHxS exposure, which was supported by histopathological changes. Additionally, PFHxS significantly reduced the humoral immune response and altered immune subsets in the spleen, suggesting immunosuppression. Gene expression changes were observed in the liver, skin, and spleen with genes involved in fatty acid metabolism, necrosis, and inflammation. Immune-cell phenotyping identified significant decreases in B-cells, NK cells, and CD11b+ monocyte/macrophages in the spleen along with increases in CD4+ and CD8+ T-cells, NK cells, and neutrophils in the skin. These findings support dermal PFHxS-induced liver damage and immune suppression. Overall, data support PFHxS absorption through the skin and demonstrate immunotoxicity via this exposure route, suggesting the need for further examination. [ABSTRACT FROM AUTHOR]

Severe negative energy balance around parturition is an important contributor to ketosis, a metabolic disorder that occurs most frequently in the peripartal period. Autophagy and mitophagy are important processes responsible for breaking down useless or toxic cellular material, and in particular damaged mitochondria. However, the role of autophagy and mitophagy during the occurrence and development of ketosis is unclear. The objective of this study was to investigate autophagy and mitophagy in the livers of cows with subclinical ketosis (SCK) and clinical ketosis (CK). We assessed autophagy by measuring the protein abundance of microtubule-associated protein 1 light chain 3-II (LC3-II; encoded by MAP1LC3) and sequestosome-1 (p62, encoded by SQSTM1), as well as the mRNA abundance of autophagy-related genes 5 (ATG5), 7 (ATG7), and 12 (ATG12), beclin1 (BECN1), and phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3). Mitophagy was evaluated by measuring the protein abundance of the mitophagy upstream regulators PTEN-induced putative kinase 1 (PINK1) and Parkin. Liver and blood samples were collected from healthy cows [n = 15; blood β-hydroxybutyrate (BHB) concentration <1.2 m M , cows with SCK (n = 15; blood BHB concentration 1.2 to 3.0 m M) and cows with CK (n = 15; blood BHB concentration >3.0 m M with clinical signs) with similar lactation numbers (median = 3, range = 2 to 4) and days in milk (median = 6, range = 3 to 9). The serum activity of aspartate aminotransferase and alanine aminotransferase was greater in cows with CK than in healthy cows. Levels of oxidative stress biomarkers malondialdehyde and hydrogen peroxide were also higher in liver tissue from ketotic cows (SCK and CK) than from healthy cows. Compared with cows with CK and healthy cows, the hepatic mRNA abundance of MAP1LC3 , SQSTM1 , ATG5 , ATG7 , ATG12 , and PIK3C3 was upregulated in cows with SCK. Compared with healthy cows, cows with SCK had a lower abundance of p62 and a greater abundance of LC3-II, but levels of both were higher in cows with CK. The mRNA abundance of ATG12 was lower in cows with CK than in healthy cows. Furthermore, the hepatic protein abundance of PINK1 and Parkin was greater in cows with SCK and slightly lower in cows with CK than in healthy cows. These data demonstrated differences in the hepatic activities of autophagy and mitophagy in cows with SCK compared with cows with CK. Although the precise mechanisms for these differences could not be discerned, autophagy and mitophagy seem to be involved in ketosis. [ABSTRACT FROM AUTHOR]

• TRAIL+ CD56bright NK cells in HBV-LC patients are highly activated. • CXCR3-related chemokines are related to the migration of TRAIL+ CD56bright NK cells to the liver. • Highly activated TRAIL+CD56bright NK cells are associated with the liver damage in HBV-LC patients. Chronic hepatitis B-related liver cirrhosis(HBV-LC)is the most common cirrhosis in China, which is characterized as liver damage and high mortality. We aim to investigate the characteristics of TRAIL+NK cells in patients with HBV-LC and their relationship with liver damage in patients with HBV-LC. Thirty cases each of chronic hepatitis B (CHB), HBV-related compensated liver cirrhosis (HBV-CLC) and HBV-related decompensated liver cirrhosis (HBV-DLC) patients were recruited in this study. Thirty age‐and sex‐matched healthy individuals were recruited as healthy controls (HCs). NK cell phenotypes were determined using flow cytometry. Serum chemokine concentrations were ascertained using the CBA Flex set. Cell apoptosis was analyzed using the Annexin V-PE/7-AAD apoptosis Kit. CD56bright NK cells increased, but CD56dim NK cells reduced in HBV-LC patients. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was mainly expressed on CD56bright NK cells. As the degree of liver damage increased, the frequency and activation of total TRAIL+NK cells and TRAIL+NK cell subsets continued to increase, especially in the HBV-LC patients. Furthermore, the difference in frequency and activation of total TRAIL+NK cells between the HBV-CLC and HBV-DLC groups was mainly due to the highly activation and increase of TRAIL+CD56bright NK cells. With the increasing degree of liver damage, CXCR3-associated chemokines (including CXCL9, CXCL10 and CXCL11) were constantly increased, particularly in the HBV-DLC group. The expression of CXCR3 on CD56bright NK cells was almost 100 % in all enrolled cohorts. CXCR3-associated chemokines were negatively correlated with liver function and positively correlated with fibrosis degree. TRAIL+CD56bright NK cells were negatively correlated with liver function, and positively correlated with fibrosis degree and CXCR3-associated chemokines. The apoptosis of K562 cells and hepatocytes was suppressed partially by the TRAIL-neutralizing antibodies. The increase of CXCR3-related chemokines (including CXCL9, CXCL10 and CXCL11) might be related to the migration of TRAIL+ CD56bright NK cells to the liver. Highly activated TRAIL+ CD56bright NK cells were associated with the liver damage in HBV-LC patients. These findings may provide new perspectives and theoretical basis for future immunotherapy of HBV-LC patients. [ABSTRACT FROM AUTHOR]

A cytokine storm conceivably contributes to manifestations of corona virus disease (COVID-19). Inflammatory cytokines such as interleukin-6 (IL-6) cause acute liver injury while serum detectability indicates systemic inflammation. We explored a link between systemic IL-6, related acute phase proteins and liver injury in hospitalized COVID-19 patients. 655 patients with suspected COVID-19 were screened in the emergency department at the University Hospital of Innsbruck, Austria, between February and April 2020. 96 patients (∼15%) were hospitalized with COVID-19. 15 patients required intensive-care treatment (ICT). Plasma aminotransferases, alkaline phosphatase, bilirubin, and gamma glutamyl transferase, as well as IL-6, C-reactive protein (CRP), ferritin and lactate dehydrogenase (LDH) were determined by standard clinical assays. Of all hospitalized COVID-19 patients, 41 (42%) showed elevated aspartate aminotransferase (AST) concentration. COVID-19 patients with elevated AST exhibited significantly higher IL-6 (p < 0.001), ferritin (p < 0.001), LDH (p < 0.001) and CRP (p < 0.05) serum concentrations compared to patients with normal AST. Liver injury correlated with systemic IL-6 (p < 0.001), CRP (p < 0.001), ferritin (p < 0.001) and LDH (p < 0.001) concentration. In COVID-19 patients requiring ICT, correlations were more pronounced. Systemic inflammation could be a fuel for hepatic injury in COVID-19. [ABSTRACT FROM AUTHOR]

The outbreak of coronavirus disease 2019 (COVID-19) starting last December in China placed emphasis on liver involvement during infection. This review discusses the underlying mechanisms linking COVID-19 to liver dysfunction, according to recent available information, while waiting further studies. The manifestations of liver damage are usually mild (moderately elevated serum aspartate aminotransferase activities), and generally asymptomatic. Few patients can still develop severe liver problems, and therapeutic options can be limited. Liver dysfunction may affect about one-third of the patients, with prevalence greater in men than women, and in elderly. Mechanisms of damage are complex and include direct cholangiocyte damage and other coexisting conditions such as the use of antiviral drugs, systemic inflammatory response, respiratory distress syndrome-induced hypoxia, sepsis, and multiple organ dysfunction. During new COVID-19 infections, liver injury may be observed. If liver involvement appears during COVID-19 infection, however, attention is required. This is particularly true if patients are older or have a pre-existing history of liver diseases. During COVID-19 infection, the onset of liver damage impairs the prognosis, and hospital stay is longer. [ABSTRACT FROM AUTHOR]

Trypanosoma evansi is a hazardous pathogenic parasite infecting a broad variety of livestock and affects wildlife worldwide. Trypanosoma evansi has gained resistance to most drugs used; therefore, it requires alternative medicines. The objective of this research was to investigate the impact of Indigofera oblongifolia leaf extract (IE) on T. evansi -induced hepatic injury. Mice were once infected with 1000 T. evansi. The treated group was gavaged with 100 mg/Kg IE after infection. Histological and biochemical changes in mice hepatic tissue were studied. Also, the oxidative damage in the liver was evaluated through determining the level of glutathione (GSH), Malondialdehyde (MDA), nitric oxide (NO) and catalase (CAT) markers. IE was able to suppress the induced parasitemia due to infection. Also, IE improved the histological liver architecture. Furthermore, the liver enzymes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) activity were improved after IE mice were treated. IE protects against hepatic damage caused by trypanosomiasis in mice. Further studies are needed to isolate the active compounds in IE and to monitor these compunds' ameliorative function. [ABSTRACT FROM AUTHOR]

Alcohol use disorder which includes alcohol abuse and dependence represents one of the leading risk factors for premature mortality in Europe and it is responsible of over 200 conditions, including neuropsychiatric disorders, chronic diseases, cancers and accidents leading to permanent disability. Alcohol use disorder represents the most common cause of liver damage in the Western world, with a wide spectrum of diseases ranging from steatosis, steatohepatitis, fibrosis, cirrhosis and cancer. The present clinical practice guidelines by the Italian Association for the Study of the Liver (AISF) are focused on the current knowledge about epidemiology, pathophysiology, clinical features, diagnosis and treatment of alcohol associated liver disease, aiming to provide practical recommendations on the management of this complex pathological condition. [ABSTRACT FROM AUTHOR]

• TNF-α producing cells are the dominant population of HBV-specific CD4 T cells in chronic HBV infection. • Increased frequency/dominance of HBV-specific IFN-γ producing CD4 T cells parallels elevated HBV viral clearance. • HBV core-specific TNF-α producing CD4 T cells are associated with liver damage in patients with a hepatitis B flare. • HBV-specific IFN-γ producing CD4 T cells are associated with HBV viral clearance in patients with a hepatitis B flare. • Some HBV-specific IFN-γ producing CD4 T cells might originate from HBV-specific TNF-α producing CD4 T cells during flare. The role of hepatitis B virus (HBV)-specific CD4 T cells in patients with chronic HBV infection is not clear. Thus, we aimed to elucidate this in patients with chronic infection, and those with hepatitis B flares. Through intracellular IFN-γ and TNF-α staining, HBV-specific CD4 T cells were analyzed in 68 patients with chronic HBV infection and alanine aminotransferase (ALT) <2x the upper limit of normal (ULN), and 28 patients with a hepatitis B flare. HBV-specific HLA-DRB1*0803/HLA-DRB1*1202-restricted CD4 T cell epitopes were identified. TNF-α producing cells were the dominant population in patients' HBV-specific CD4 T cells. In patients with ALT <2xULN, both the frequency and the dominance of HBV-specific IFN-γ producing CD4 T cells increased sequentially in patients with elevated levels of viral clearance: HBV e antigen (HBeAg) positive, HBeAg negative, and HBV surface antigen (HBsAg) negative. In patients with a hepatitis B flare, the frequency of HBV core-specific TNF-α producing CD4 T cells was positively correlated with patients' ALT and total bilirubin levels, and the frequency of those cells changed in parallel with the severity of liver damage. Patients with HBeAg/HBsAg loss after flare showed higher frequency and dominance of HBV-specific IFN-γ producing CD4 T cells, compared to patients without HBeAg/HBsAg loss. Both the frequency and the dominance of HBV S-specific IFN-γ producing CD4 T cells were positively correlated with the decrease of HBsAg during flare. A differentiation process from TNF-α producing cells to IFN-γ producing cells in HBV-specific CD4 T cells was observed during flare. Eight and 9 HBV-derived peptides/pairs were identified as HLA-DRB1*0803 restricted epitopes and HLA-DRB1*1202 restricted epitopes, respectively. HBV-specific TNF-α producing CD4 T cells are associated with liver damage, while HBV-specific IFN-γ producing CD4 T cells are associated with viral clearance in patients with chronic HBV infection. TNF-α producing cells are the dominant population of hepatitis B virus (HBV)-specific CD4 T cells in patients with chronic HBV infection. This population of cells might contribute to the aggravation of liver damage in patients with a hepatitis B flare. HBV-specific IFN-γ producing CD4 T cells are associated with HBV viral clearance. Differentiation from HBV-specific TNF-α producing CD4 T cells into HBV-specific IFN-γ producing CD4 T cells might favor HBV viral clearance. [ABSTRACT FROM AUTHOR]

Cisplatin (CP) is an active cytotoxic agent, which has been verified to be effective in multiple cancer regimen. In this study, potential antioxidant effects of casticin (CAS) were assessed against CP generated oxidative stress in rat liver. "Twenty-four male Sprague Dawley rats were divided into four experimental groups. Group-1 (control group) received only normal saline". Group-2 was intraperitoneally injected with CP (10 mg/kg). Group-3 was orally provided by CAS (50 mg/kg) along with CP (10 mg/kg) injection at first day. Group-4 group was orally administered with CAS (50 mg/kg) throughout the experiment. The rats of group-1 indicated "increase in serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), while a significant decrease in the activities of catalase (CAT), superoxide dismutase (SOD) and peroxidase (POD)" was noticed, which revealed that CP generated oxidative stress in rat liver. Moreover, administration of CP increased the hydrogen peroxide (H 2 O 2) concentration and level of "thiobarbituric acid reactive substances (TBARS)", while reducing the % DNA head and head length in liver cell nuclei. CP disturbs the lobular structure of the liver and increased the sinusoidal dilation in rat liver. However, co-treatment with CAS successfully mitigated the CP generated DNA disruption, biochemical and pathological changes in rat liver. These findings revealed that an effective antioxidant, CAS, alleviated the CP generated hepatotoxicity and oxidative stress in rats. [ABSTRACT FROM AUTHOR]

The obesity epidemic, especially in pregnant women, linked to a higher risk of liver diseases. Bile acids (BAs) are known to participate in liver metabolism, but this function during obesogenic reproductive process remains largely uncertain. The study aims to identify whether a high-fat diet (HFD) during pregnancy negatively disturbs liver metabolism and the potential role of BAs and gut microbiota (GM)in a sow model. Reproductive (RP) or non-reproductive (NRP) sows were fed a 15 % HFD containing compound oil. Body condition, blood parameters, and BAs levels/profile during gestation and lactation were monitored. The tissues and colonic GM were collected after euthanasia at the end of lactation. HepG2 hepatocytes were used to test the effects of BAs on liver damage and the mechanism. Reproductive sows fed an HFD (HF-RP) experienced increased weight loss, and elevated plasma non-esterified fatty acid (NEFA) during lactation, consistent with exacerbated lipolysis, aggravating the risk of liver damage. HF-RP sows exhibited an enlarged BAs pool size and alterations in composition (higher levels of CDCA and LCA species) along with a drastic change in the GM (increased Firmicutes / Bacteroidetes ratio and declined Lactobacillus abundance). Furthermore, the liver FXR-SHP pathway, BAs synthesis and transport underwent adaptive regulation to sustain the BAs homeostasis and hepatic lipid metabolism. CDCA alleviated endoplasmic reticulum (ER) stress induced by palmitic acid via FXR pathway, in HepG2 cells. Lactation BAs metabolism signal in gut-liver axis coordinated the risk of liver damage induced by exacerbated lipolysis in obesogenic pregnancy. • HFD enhances postpartum lipolysis and circulation NEFA, exacerbating liver damage. • Lactation-enlarged BA pools, especially CDCAs, are adaptive to liver lipid homeostasis. • HFD and reproductive state shift the gut microbiota toward increased LCAs production. • CDCA alleviates endoplasmic reticulum (ER) stress induced by palmitic acid via FXR pathway in HepG2 cells. [ABSTRACT FROM AUTHOR]

Recently, carbon quantum dots (CQDs) have become popular because of their simple synthesis and potential applications. Although CQDs have high biocompatibility, their biotoxicity must be verified to reduce the possible risks associated with large-scale application. In this study, the hepatotoxicity of three CQD types, namely diammonium citrate (AC)-based (CQDs-AC), spermidine trihydrochloride (Spd)-based (CQDs-Spd), and AC- and Spd-based CQDs (CQDs-AC/Spd), were evaluated in vivo and in vitro. It was observed in vivo that CQDs-Spd and CQDs-AC/Spd, but not CQDs-AC, caused histopathological damage, including liver steatosis and mild mixed inflammatory cell infiltration; however, reduced liver function was only observed in CQD-Spd–treated mice. The in vitro results revealed that only CQDs-Spd significantly decreased the number of viable HepG2 cells (NADH depletion) and induced oxidative stress (heme oxygenase-1 activation) after 24 h of exposure, which promoted inflammatory factor secretion (NF-κB activation). Additionally, decreasing zonula occludens-2 and α1-antitrypsin protein expression in HepG2 cells suggested that CQD-Spd exposure increases the risk of liver diseases. Our results revealed that CQDs-Spd had greater hepatotoxic potential than CQDs-AC and CQDs-AC/Spd, which might be attributable to their high positive surface charge. Overall, the risk of CQD-induced hepatotoxic risk must be considered when applying positively charged CQDs. [Display omitted] • CQDs-Spd can induce histopathological harm and impair liver function. • CQDs-Spd initiates pronounced oxidative cytotoxicity. • CQDs-Spd triggers heightened inflammatory responses. • CQDs-Spd may accelerate the initial stages of liver disease. • Exposure to positively charged surface CQDs can impact hepatic well-being. [ABSTRACT FROM AUTHOR]

Cymbopogon jwarancusa (Jones) Schult. (Family: Poacea/Gramineae) is being used to treat numerous ailments in traditional/folklore and indigenous system of medicine due to its antioxidant, anti-allergic, antiparasitic, analgesic, antipyretic and anticancer activities; however there is no documented evidence regarding its hepatoprotective efficacy. This study was aimed to evaluate hepatoprotective activity of hydroalcoholic extract of Cymbopogon jwarancusa (HECJ) against paracetamol (PCM) induced liver damage in albino Wistar rats, and to identify the bioactive components present in the extract responsible for the said activity. Five groups of rats (n = 6) were orally treated with: 0.5% carboxymethyl cellulose (normal control), 50 mg/kg silymarin (reference standard), HECJ [515 mg/kg (low dose) and 720 mg/kg (high dose)] (test groups) for 7 days daily, followed by induction of hepato-toxicity using PCM (2 gm/kg) on 7th day (PCM control; reference standard; test groups). The blood samples to estimate the level of AST, ALT, ALP, total bilirubin and total protein; liver tissue homogenate for antioxidant markers (GSH, GST, GPx, and LPO) and liver section for histopathological analysis were collected. Isolation and characterization of phytochemicals from HECJ was done by preliminary screening, determination of phenolic, flavonoid and terpenoid content, and GC-MS analysis. The animals pre-treated with HECJ dose-dependently and significantly alleviated the PCM-induced alterations in liver enzymes, plasma proteins, serum total bilirubin and antioxidant markers levels. The histopathological analysis suggest that PCM causes marked necrosis and lymphocyte infiltration, while preservation of the normal hepatic architecture was observed in groups pre-treated with, reference standard drug silymarin, and HECJ. Preliminary screening of the extract, determination of phenolic, flavonoid and terpenoid content, and GC-MS analysis revealed the presence of some important bioactive components such as phenolics, flavonoids, glycoside, tannins, steroids, fatty acids, sterols, esters, saponins, terpenes/terpenoids and essential oil which could be synergistically responsible for the plant's hepatoprotective effect. This study concluded that C. jwarancusa could be taken as a beneficial natural product for its hepatoprotective efficacy; however, future line of work is required to establish its precise mechanism of action. [Display omitted] • The current study reports the first ever detailed hepatoprotective evaluation of ethnomedicinal plant Cymbopogon jwarancusa (Jones) Schult and also a first study to identify the bioactive components present in its hydroalcoholic extract responsible for the said activity. • The hydroalcoholic extract of Cymbopogon jwarancusa (HECJ) exerts significant hepatoprotective effect in rats in a dose-dependent manner. • Administration of HECJ significantly drifts liver enzymes (AST, ALT, and ALP), plasma proteins, serum total bilirubin and antioxidant markers (GSH, GST, GPx and LPO) levels towards normal and restores liver architecture. • Isolation and characterization of the bioactive components exhibits the presence of phenolics, flavonoids, glycoside, tannins, steroids, fatty acids, sterols, esters, saponins, terpenes/terpenoids and essential oil which could possibly be responsible for the plant's hepatoprotective effect. [ABSTRACT FROM AUTHOR]

Chronic exposure to arsenic remains a major environmental public health concern worldwide, affecting hundreds of millions of people. Arsenic-induced multiorgan damage and miRNA expression changes after arsenic exposure have been determined, but their associations and risks have not been fully examined. In this study, we measured the expression levels of five miRNAs in plasma from control and arsenic poisoned populations, and we analyzed the relationship between miRNAs and multiorgan damage. The results clearly show that the upregulation of miR-155 expression can increase the risk of arsenic induced skin damage (OR = 10.55; 95% CI: 6.02, 18.47); further, there is a link between the expression of miR-21 (OR = 11.84; 95% CI: 5.34, 26.28) and miR-145 (OR = 2.39; 95% CI: 1.61, 3.55) and liver damage, and miR-191 and kidney damage (OR = 3.65; 95% CI: 1.49, 8.93). In addition, we analyzed the diagnostic value of miRNAs associated with specific organ damage in arsenic-induced multiorgan damage. It was found that the miR-155 has a certain diagnostic value in arsenic-induced skin damage (AUC = 0.83), miR-21 and miR-145 have diagnostic value for liver damage (AUC = 0.80, 0.81) and miR-191 has diagnostic value for kidney damage (AUC = 0.83). This study provides the first comprehensive assessment of the association and risk of five miRNAs with arsenic-induced multiorgan damage. The study can provide a scientific basis for further understanding the causes of arsenic-induced multiorgan damage, identification of possible biological markers, and improvement of targeted prevention and control strategies. Unlabelled Image • Upregulation of miR-155 can increase the risk of arsenic induced skin damage. • Upregulation of miR21 and miR145 can increase the risk of arsenic induced liver damage. • Upregulation of miR191 can increase the risk of arsenic induced kidney damage. • miR21, miR145, miR155, miR191 has diagnostic value for corresponding organ damage. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate whether the antiparasitic drug eprinomectin causes hepatic oxidative stress and impairment of hepatic energetic metabolism in the silver catfish (Rhamdia quelen), in conditions of experimental aquatic contamination. The fish were exposed for 24 and 48 h at various concentrations of eprinomectin (0.0, 1.124, 1.809 and 3.976 μg L−1), followed by 48 h of recovery in eprinomectin-free water. We measured levels of reactive oxygen species (ROS) and lipoperoxidation (LOOH) in hepatic tissue, as well as levels of antioxidant capacity against peroxyl radicals (ACAP), and activities of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase (GST), in addition to the activities of enzymes involved in energy metabolism, adenylate kinase (AK) and pyruvate kinase (PK). After 24 h, hepatic ROS levels increased in fish exposed to all concentrations of eprinomectin, and the same occurred with LOOH at the two highest concentrations of eprinomectin. ACAP levels decreased after 24 h of exposure to the highest concentration, also occurring with SOD activity at the two highest concentrations. Glutathione enzymes activities (GPx and GST) decreased after 48 h of exposure to the highest concentration. Fish transfer to eprinomectin-free water, with re-analysis after 48 h post-recovery, was unable to reverse ROS and LOOH increases, likewise with the reductions of ACAP, SOD, GPx and GST, especially at the two highest concentrations. AK and PK activities decreased after 48 h of exposure, AK decreased at the two highest concentrations and PK decreased at the highest concentration. AK activity remained lower after 48 h in eprinomectin-free water. PK activity returned to normal after 48 h in eprinomectin-free water. In summary, silver catfish exposed to aquatic contamination with the antiparasitic drug eprinomectin showed hepatic oxidative stress, possibly related to impairment of the phosphotransfer network and energy metabolism. • Eprinomectin is a dangerous contaminant for aquatic organisms. • Eprinomectin reduced the activity of the hepatic antioxidant defense system in fish. • Eprinomectin caused oxidative stress in the liver of fish. • Eprinomectin impaired the phosphotransfer network and energy metabolism in the liver of fish. • Eprinomectin disrupted hepatic homeostasis. [ABSTRACT FROM AUTHOR]

Abstract Lysosomal acid lipase (LAL) hydrolyzes cholesteryl esters (CE) and triglycerides (TG) to generate fatty acids (FA) and cholesterol. LAL deficiency (LAL-D) in both humans and mice leads to hepatomegaly, hypercholesterolemia, and shortened life span. Despite its essential role in lysosomal neutral lipid catabolism, the cell type-specific contribution of LAL to disease progression is still elusive. To investigate the role of LAL in the liver in more detail and to exclude the contribution of LAL in macrophages, we generated hepatocyte-specific LAL-deficient mice (Liv-Lipa −/−) and fed them either chow or high fat/high cholesterol diets (HF/HCD). Comparable to systemic LAL-D, Liv-Lipa −/− mice were resistant to diet-induced obesity independent of food intake, movement, and energy expenditure. Reduced body weight gain was mainly due to reduced white adipose tissue depots. Furthermore, Liv-Lipa −/− mice exhibited improved glucose clearance during glucose and insulin tolerance tests compared to control mice. Analysis of hepatic lipid content revealed a massive reduction of TG, whereas CE concentrations were markedly increased, leading to CE crystal formation in the livers of Liv-Lipa −/− mice. Elevated plasma transaminase activities, increased pro-inflammatory cytokines and chemokines as well as hepatic macrophage infiltration indicated liver inflammation. Our data provide evidence that hepatocyte-specific LAL deficiency is sufficient to alter whole-body lipid and energy homeostasis in mice. We conclude that hepatic LAL plays a pivotal role by preventing liver damage and maintaining lipid and energy homeostasis, especially during high lipid availability. Graphical abstract Unlabelled Image Highlights • Generation of hepatocyte-specific Lipa-deficient mice • Hepatic cholesteryl ester accumulation in Liv-Lipa −/− mice • Improved glucose tolerance and resistance to diet-induced obesity • Hepatic inflammation and liver fibrosis in Liv-Lipa −/− mice • Hepatocyte-specific LAL is critical for maintaining lipid and energy homeostasis. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the specificity and sensitivity of real-time ultrasound elastography (RTE) in the evaluation of liver damage induced by brain death and the correlation with ultrastructural changes in liver tissue. Eleven RTE parameters before brain death and at 0, 3, 6 and 9 h after brain death in 12 miniature pigs were collected and analyzed, and the correlation of these parameters with electron microscopy results was explored. Six of the RTE parameters, namely, mean relative strain value within the region of interest, standard deviation of the relative strain value within the region of interest, area of low strain within the region of interest, complexity of low strain area within the region of interest, skewness and correlation, significantly differed among the time periods. Categorical data were analyzed using the χ2-test. Spearman's correlation analysis was used for evaluating correlations between RTE parameters and electron microscopy results, and the correlation coefficients (r) were calculated. Electron microscopy results revealed that liver damage gradually increased after brain death, with significant differences between 0 and 9 h (χ2 = 14.143, p value = 0.027). In addition, the six aforementioned RTE parameters significantly correlated with electron microscopy results, with the mean relative strain value within the region of interest being the strongest (r = -0.59, p value < 0.001) correlated parameter. RTE could provide preliminary assessment of liver damage induced by brain death, and correlates to ultrastructural changes in liver tissue. [ABSTRACT FROM AUTHOR]

Abstract Bilirubin is predominantly formed in the liver as a result of breakdown of hemoglobin. Knowing the concentration of bilirubin in serum is important in evaluating the health of the liver, and for the diagnosis of hyperbilirubinemia (a condition that afflicts approximately 60% of full-term and 80% of pre-term newborns). This paper describes the design and fabrication of a potentiometric sensor for the determination of free bilirubin in serum. The sensor has a polymeric ion-selective membrane, and selectively measures free ionic bilirubin ("unbound" bilirubin – i.e., bilirubin not complexed to albumin or other complexing agents), in the presence of other anions — chloride, phosphate, pyruvate, deoxycholate, and lactate — also present in serum. The linear response range of the sensor (1.0 mM to 0.10 μM bilirubin, measured in a sodium phosphate buffer with pH 8.6) covers the clinically-relevant concentration of bilirubin in serum (5–500 μM). Free bilirubin could be detected in human blood serum with this potentiometric sensor. The components of the potentiometric bilirubin sensor were embedded in a paper-based device to provide a sensor that is disposable and easy to use, and thus is suitable for applications at the point-of-care. The paper-based potentiometric bilirubin sensor exhibited a response range of 5.0–0.10 mM (sufficient to cover the clinically-relevant concentration of bilirubin in serum). Only 15 μL of sample is required for measurement of the concentration of free bilirubin, and the analysis can be performed in less than two minutes. Highlights • A potentiometric sensor was developed for the detection of free bilirubin in blood serum. • The sensor displayed significant selectivity for free bilirubin in the presence of common anions in serum. • The components of the sensor were embedded in a paper-based device to demonstrate applicability in performing point-of-care measurements. [ABSTRACT FROM AUTHOR]

Abstract Melatonin is a neurohormone associated with sleep and wakefulness and is mainly produced by the pineal gland. Numerous physiological functions of melatonin have been demonstrated including anti-inflammation, suppressing neoplastic growth, circadian and endocrine rhythm regulation, and its potent antioxidant activity as well as its role in regeneration of various tissues including the nervous system, liver, bone, kidney, bladder, skin, and muscle, among others. In this review, we summarize the recent advances related to the multiple protective roles of melatonin receptor agonists, melatonin and N-acetylserotonin (NAS), in brain injury, liver damage, and bone health. Brain injury, including traumatic brain injury, ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and newborn perinatal hypoxia-ischemia encephalopathy, is a major cause of mortality and disability. Liver disease causes serious public health problems and various factors including alcohol, chemical pollutants, and drugs induce hepatic damage. Osteoporosis is the most common bone disease in humans. Due in part to an aging population, both the cost of care of fracture patients and the annual fracture rate have increased steadily. Despite the discrepancy in the pathophysiological processes of these disorders, time frames and severity, they may share several common molecular mechanisms. Oxidative stress is considered to be a critical factor in these pathogeneses. We update the current state of knowledge related to the molecular processes, mainly including anti-oxidative stress, anti-apoptosis, autophagy dysfunction, and anti-inflammation as well as other properties of melatonin and NAS. Particularly, the abilities of melatonin and NAS to directly scavenge oxygen-centered radicals and toxic reactive oxygen species, and indirectly act through antioxidant enzymes are disscussed. In this review, we summarize the similarities and differences in the protection provided by melatonin and/or NAS in brain, liver and bone damage. We analyze the involvement of melatonin receptor 1A (MT1), melatonin receptor 1B (MT2), and melatonin receptor 1C (MT3) in the protection of melatonin and/or NAS. Additionally, we evaluate their potential clinical applications. The multiple mechanisms of action and multiple organ-targeted properties of melatonin and NAS may contribute to development of promising therapies for clinical trials. Graphical abstract fx1 Highlights • Melatonin and NAS are protective agents for brain injury, liver damage and bone health. • Melatonin and NAS are anti-oxidative stress and anti-inflammation. • Melatonin and NAS are against autophagy dysfunction and anti-apoptosis. • MT1/MT2 are needed for brain and liver injuries and MT2 is important for bone health. • Melatonin and NAS will be likely to show utility in clinical trials. [ABSTRACT FROM AUTHOR]

Aflatoxin B1 (AFB1) is very harmful for broiler production and public health. The water-soluble castoff in gluten production, i.e. the water-soluble substances of wheat (WSW) that contains 14% pentosan has positive effect on animal nutrient absorption, immunity, and antioxidation. Our study aims to investigate the preventive effects of WSW against AFB1-induced broiler liver injury. One day-old Arbor Acres broilers were randomly separated to 4 groups and were, respectively, fed with control diet, diet with 5 mg/kg AFB1 standard, diet with 5 mg/kg AFB1 standard and 214 ml/kg WSW, and diet with 214 ml/kg WSW continuously for 28 d. The histopathological, ultra-structural, and serological changes were tested to evaluate liver damage. The hallmarks of hepatocellular autophagy, apoptosis, and inflammation were measured by Western Blot and real-time polymerase chain reaction. The content of AFB1 in chicken liver was detected with an ultra-high performance liquid chromatography linked with the fluorescence detection method. The results showed that (i) WSW restored AFB1-induced changes in serum biochemical parameters, and ameliorated histomorphological changes in hepatocytes, (ii) WSW reduced the content of AFB1 in chicken liver, (iii) WSW alleviated AFB1-induced autophagy inhibition by up-regulating hepatic LC3, beclin-1, and down-regulating hepatic mTOR and cytoplasmic P53 expressions, (iv) WSW alleviated AFB1-induced hepatocellular apoptosis via inhibiting pro-apoptotic gene expression (nuclear P53, Caspase3, Bax), and promoting anti-apoptotic gene expression (bcl-2), (v) WSW feeding ameliorated AFB1-induced liver inflammation via impeding TLR4/NF- |${{\bf \kappa }}$| B and IL-1/NF- |${{\bf \kappa }}$| B signaling pathways, down-regulating pro-inflammatory cytokines (IL-1 |${{\bf \beta }}$|⁠, IL-6, and IL-8), and markedly up-regulating anti-inflammatory genes (IL-10 and HO-1). Conclusively, WSW is a potential preventer of AFB1-induced broiler liver damage by reducing the AFB1 content in liver, accelerating hepatocellular autophagy and inhibiting hepatocytes apoptosis and liver inflammation. [ABSTRACT FROM AUTHOR]

Citrus pectin has been proved for its ability to bind heavy metals from industrial wastewater. However, few studies have investigated the detoxification effect of citrus pectin on cadmium-induced damage through in vivo experiments. In this study, pectin was extracted from fingered citron peel and subjected to pH-temperature modification, and successful modification of pectin's molecular structure was confirmed by a decrease in the degree of esterification and the increase in the content of free carboxylate groups in the structure. In vitro studies suggested that the modified fingered citron peel pectin (mFCPP) showed higher cadmium removal ability compared to unmodified fingered citron peel pectin (FCPP). A 20-week study in cadmium-exposed mice suggested significant improvement in liver and kidney function with co-treatment of pectin. Co-treatment with FCPP or mFCPP ameliorated the cadmium-induced cell death and oxidative damage in the liver and kidney. Moreover, the study demonstrated that both FCPP and mFCPP were impermeable through the intestinal wall, suggesting their binding with the cadmium ions in the gastrointestinal tract, thus preventing cadmium ions absorption and entry into the systemic circulation. [Display omitted] • Finger citron peel pectin (FCPP) is modified with pH- and temperature-modification. • Modified Finger citron peel pectin (mFCPP) has a stronger cadmium removal ability. • FCPP and mFCPP protect liver and kidney of mice from Cd-induced toxicity. • FCPP and mFCPP prevent Cd from being absorbed in the intestinal of mice. [ABSTRACT FROM AUTHOR]

Exposure to cadmium (Cd), an environmental heavy metal contaminant, is a serious threat to global health that increases the burden of liver diseases. Autophagy and apoptosis are important in Cd-induced liver injury. However, the regulatory mechanisms involved in the progression of Cd-induced liver damage are poorly understood. Herein, we investigated the role of vacuolar protein sorting 41 (VPS41) in Cd-induced autophagy and apoptosis in hepatocytes. We used targeted VPS41 regulation to elucidate the mechanism of Cd-induced hepatotoxicity. Our data showed that Cd triggered incomplete autophagy by downregulating VPS41, aggravating Cd-induced hepatocyte apoptosis. Mechanistically, Cd-induced VPS41 downregulation interfered with the mTORC1-TFEB/TFE3 axis, leading to an imbalance in autophagy initiation and termination and abnormal activation of autophagy. Moreover, Cd-induced downregulation of VPS41 inhibited autophagosome–lysosome fusion, leading to blocked autophagic flux. This triggers incomplete autophagy, which causes excessive P62 accumulation, accelerating Caspase-9 (CASP9) cleavage. Incomplete autophagy blocks clearance of cleaved CASP9 (CL-CASP9) via the autophagic pathway, promoting apoptosis. Notably, VPS41 overexpression alleviated Cd-induced incomplete autophagy and apoptosis, independent of the homotypic fusion and protein sorting complex. This study provides a new mechanistic understanding of the relationship between autophagy and apoptosis, suggesting that VPS41 is a new therapeutic target for Cd-induced liver damage. [Display omitted] • Cd induces incomplete autophagy by downregulating VPS41. • Cd activates autophagy via the VPS41-mTORC1-TFEB/TFE3 axis. • VPS41 overexpression alleviates Cd-caused inhibition of autophagosome-lysosome fusion. • P62 accumulation from incomplete autophagy promotes CASP9-mediated apoptosis. • Cd imbalances the initiation/termination of autophagy and autophagy-apoptosis. [ABSTRACT FROM AUTHOR]

[Display omitted] • 1,2-diacetylbenzene (DAB) induced liver dysfunction, and risperidone alleviated it. • DAB activates TLR4/JNK/NF-κB and Jak2/Stat5, and apoptosis pathways. • DAB inhibits the Jak2/Stat3 and IRS1/PI3K/AKT/MDM2 signaling pathways. • Stat3, miR-26b-5p/34a-5p, NFKB1, and liver cirrhosis were key findings in silico analysis. • Key biological activity: hepatitis (for DAB) and immunomodulator (for risperidone). 1,2-Diacetylbenze (C 10 H 10 O 2 , DAB) is a potential inducer or activator of toxic mechanisms. DAB exerts high absorption by the gastrointestinal tract and high blood–brain barrier penetration. However, only the effects of DAB on the central nervous system were reported, with a dearth of evidence of DAB's effects on the liver, which is more susceptible to toxic substances. Risperidone, an atypical antipsychotic drug, has been shown to protect against DAB-induced cognitive impairment in an animal model. Risperidone was found to have little or no effect on the liver after short-term administration. The question of whether risperidone can protect against DAB-induced liver dysfunction, particularly after short-term administration, is unknown. Thus, this study aimed to assess the hepatoprotective effects of risperidone on DAB-induced liver dysfunction in male C57BL/6 mice treated with DAB 5 mg/kg for 1 week and risperidone 0.125–0.25 mg/kg for 2 weeks. After exposure to DAB 5 mg/kg for 1 week, we found that DAB induced liver damage by increasing liver function biomarkers (GGT, ALT, and AST), reactive oxygen species, nitric oxide, and proinflammatory cytokines (IL-1α, IL-1β, IL-6, IL-12, and TNF- α), activating apoptosis (elevated Caspase-3 and Bax levels and reduced Bcl2 level), TLR4/JNK/NF-κB, Jak2/Stat5 pathways, and suppressing Jak2/Stat3 and IRS1/PI3K/AKT/MDM2 pathways. After a 2-week course of treatment, risperidone was able to lessen these effects; the higher dose (0.25 mg/kg) appeared to be more effective than the lower dose (0.125 mg/kg). To strengthen findings from in vivo analysis, in silico analysis also found three targets (Stat3, Caspase-3, AKT, IL-1β), two miRNAs (miR-26b-5p and miR-34a-5p), two transcription factors (NFKB1 and NFKB2), and numerous pathways ("AGE-RAGE signaling pathway in diabetic complications", "hepatitis B", "alcoholic liver disease", "apoptosis", and "liver cirrhosis") as the key molecular processes involved in the pathogenesis of DAB-induced liver damage and targeted by risperidone. The physicochemical characteristics and pharmacokinetics of DAB and risperidone also support the toxic effects of DAB and the beneficial properties of risperidone in the liver. In conclusion, these findings reflect the therapeutic effects of risperidone on DAB-induced liver dysfunction after 1 week and 2 weeks exposure to DAB and risperidone, respectively. [ABSTRACT FROM AUTHOR]

[Display omitted] • Real indoor VOC disturbed liver lipid metabolism, characterized by the decreased TG and DG. • Machine learning identified five serum biomarkers for liver lipid metabolism disorders. • Dual-omics analysis revealed the upregulated Dgkq as crucial regulator for TG reduction. • VOC downregulated FoxO, thus promoting Dgkq upregulation in lipid metabolism. As a widespread indoor air pollutant, volatile organic compound (VOC) caused various adverse health effects, especial the damage to liver, which has become a growing public concern. However, the current toxic data are intrinsically restricted in the single or major VOC species. Limited knowledge is available regarding toxic effects, biomarkers and underlying mechanisms of real indoor VOC-caused liver damage. Herein, an indoor relevant VOC exposure model was established to evaluate the hepatic adverse outcomes. Machine learning and multi-omics approaches, including liver lipidomic, serum lipidomic and liver transcriptomic, were utilized to uncover the characteristics of liver damage, serum lipid biomarkers, and involved mechanism stimulated by VOC exposure. The result showed that indoor relevant VOC led to the abnormal hepatic lipid metabolism, mainly manifested as a decrease in triacylglycerol (TG) and its precursor substance diacylglycerol (DG), which could be contributed to the occurrence of hepatic adverse outcomes. In terms of serum lipid biomarkers, five lipid biomarkers in serum were uncovered using machine learning to reflect the hepatic lipid disorders induced by VOC. Multi-omics approaches revealed that the upregulated Dgkq disturbed the interconversion of DG and phosphatidic acid (PA), leading to a TG downregulation. The in-depth analysis revealed that VOC down-regulated FoxO transcription factor, contributing to the upregulation of Dgkq. Hence, this study can provide valuable insights into the understanding of liver damage caused by indoor relevant VOC exposure model VOC exposure, from the perspective of multi-omics analysis. [ABSTRACT FROM AUTHOR]

Doxorubicin (DXR) is widely used in cancer treatment. However, it has not yet been possible to prevent the side effects of DXR. The aim of this study was to investigate the hepatoprotective effect of crocin against DXR used in cancer treatment. For this reason; forty Wistar rats (male-250–300 g) were allocated into four groups (n = 10/group): Control, Crocin, DXR and DXR+Crocin. Control and Crocin groups were administered saline and crocin (40 mg/kg, i.p) for 15 days, respectively. DXR group, cumulative dose 12 mg/kg DXR, was administered for 12 days via 48 h intervals in six injections (2 mg/kg each, i.p). DXR+Crocin group, crocin (40 mg/kg-i.p) was administered for 15 days, and DXR was given as in the DXR group. The results revealed that serum liver markers (alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) increased significantly after DXR administration but recovered after crocin therapy. In addition, lipid peroxidation (MDA), and inflammatory cytokine (TNF-α) increased after DXR application and the antioxidative defense system (GSH, SOD, CAT) significantly decreased and re-achieved by crocin treatment. Our results conclude that crocin treatment was related to ameliorated hepatocellular architecture and reduced hepatic oxidative stress and inflammation in rats with DXR-induced hepatotoxicity. • Doxorubicin injection caused a deterioration in the liver oxidant/antioxidant balance. • Hepatotoxicity was demonstrated by histopathologicaly and immunohistochemically. • Doxorubicin upregulated alpha-smooth muscle actin (α-SMA) and inflammation. • Crocin treatment ameliorated impaired liver oxidant/antioxidant balance. • Crocin reduced α-SMA, and promoted improvement of hepatocellular architecture. [ABSTRACT FROM AUTHOR]

Abstract In order to compare the detailed toxicity of nano‑copper and CuCl 2 ·2H 2 O (Cu ions) in vivo , the oral toxicity of four differently sized Cu particles (30 nm, 50 nm, 80 nm and 1 μm) on rats was investigated compared with CuCl 2 ·2H 2 O in acute exposure scenarios. We compared the acute LD 50 values and evaluated the kinetics of Cu following a single equivalent dose (200 mg/kg) of five Cu materials. Continuous gavage of nano‑copper for 7 days, the mortality rates, relative organ weights, and hematological, biochemical, and histopathologic characteristics of rats were examined. The results showed that the LD 50 values of Cu ions, 30 nm, 50 nm, 80 nm, and 1 μm copper particles were 359.6, 1022, 1750, 2075, and >5000 mg/kg, respectively. Physiological and biochemical indexes indicated that 80 nm nano‑copper (Cu NPs) produced the highest degrees of toxicity in short term. The liver and kidneys were the major organs most affected by Cu NPs, and also the target organs for Cu accumulation. The toxic effects of Cu ions are similar to those of nano‑copper, but they were not the same. Therefore, the toxic effect of nano‑copper is likely to be the result of the dual action of nano‑copper particles and copper ions. Collectively, the acute toxic effects produced by Cu NPs were highly correlated with particle size. Moreover, the toxic effects produced by repeated dosing differed from those produced by a single dose, and this may be due to organ targeting effects that are dependent on the size of the nano-particles. Highlights • The acute toxicity of Cu ions, 30 nm, 50 nm, 80 nm and 1 μm copper particles were compared and LD 50 decreased with decreasing particle size. • The liver and kidney were the main organs for the toxicity and accumulation of Cu NPs. • Particle size is one of the key factors affecting the toxicity of Cu NPs, but 80 nm Cu NPs leads to the strongest short-term toxicity. [ABSTRACT FROM AUTHOR]

Iron is a vital element required for normal cellular physiology in animal systems, but excess iron accumulation in the biological system accelerates oxidative stress, cellular toxicity, tissue injury and organ fibrosis, which ultimately leads to the generation of chronic liver diseases including cancer. A natural antioxidant, ellagic acid (EA) has been previously reported for its pharmacological properties; however, there is no significant evidence available that could illustrate its protective potential against iron-overload induced hepatotoxicity. In the present work, EA was evaluated for its in vitro free radical scavenging and iron chelation potentials. Further, EA was tested in vivo for its protective activity against iron overload-induced hepatotoxicity in Swiss albino mice by evaluating liver iron content, reactive oxygen species (ROS), liver antioxidant enzymes, serum marker levels, liver damage and fibrosis, histopathological study and finally western blotting analysis. EA treatment significantly decreased liver iron and serum ferritin levels. Elevated ROS levels, decreased antioxidant parameters and elevated serum markers were normalized upon treatment with EA. Cellular morphology, iron -overload and liver fibrosis were found to be effectively ameliorated. Finally, the protective effect of EA against iron overload-induced apoptosis was confirmed by western blotting when its treatment upregulated the expressions of caspase-3 and poly(ADP-ribose) polymerase (PARP) proteins. EA revealed hepatoprotective activity against iron overload-induced toxicity through scavenging free radicals, inhibiting excess ROS production, normalizing liver damage parameters and upregulating caspase-3, PARP expression. Collectively, our findings support the possible use of the natural antioxidant EA as a promising candidate against iron-overloaded diseases. [ABSTRACT FROM AUTHOR]

Summary Objectives The purpose of this study was to investigate the redox status in professional football players during a championship period consisting of two games interspersed with low-intensity training. Methods The collection of blood and saliva began at the start of a championship tournament that followed a week without any strenuous activity after a full season of games. Six collections were performed: (1) basal; (2) post-game one (day 2); (3) 48 h post-game-one (day 4); (4) post-game two (day 6); (5) 24 h post-game two (day 7); and (6) 48 h post-game two (day 8). Results Damage to liver was suggested by increased levels of γ-glutamyl transferase (∼47%; P < 0.05), but only 48 h post-game two. The redox balance was also affected, since uric acid was increased (90%) post-game two for 24 h (P < 0.05) and the ratio of reduction to oxidized glutathione decreased after post-game one until 48 h after game two (4.05 ± 1.7 basal; 0.34 ± 0.07 48 post-game two). In plasma, creatine kinase (CK) levels increased two-fold after the first game (79 to 216 IU/L) suggesting muscle damage and remained elevated throughout the period of the study. Conclusion The results show a significant increase in oxidative stress during a week of professional activity spanning 2 games in professional football players suggesting that the conventional recovery period between games is not sufficient to prevent muscle and liver cells damage. [ABSTRACT FROM AUTHOR]

We investigated the effects of induced spawning on liver and blood cell changes in matrinxã breeders, a commercially valuable South American fish that requires hormonal manipulation and stripping to spawn, a trait shared by other important aquaculture species. Little attention has been given to this topic despite the mortality rates commonly reported by fish farmers following this practice. In this study, we show that the overall handling required in induced spawning severely impaired the liver (hypertrophy of the hepatocytes, enlargement of the cell nuclei and reductions of glycogen deposits) which was mainly attributed to hormonal therapy. Additionally, the induced spawning procedure increased the number of red blood cells and decreased the white blood cell and thrombocyte count. These results corroborate the stressful conditions and immunosuppression, which together with the liver damage may explain the reported mortality rates. Finally, our findings outline important approaches for improving induced spawning technique. [ABSTRACT FROM AUTHOR]