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Tamoxifen (TAM) is extensively used to manage estrogen receptor-positive breast cancer. Despite its effectiveness, its administration can negatively impact various organs, including the liver. This research focused on the effects of TAM on the pyroptotic pathway in the liver and evaluated the potential of cardamom extract (CRDE) to lessen hepatic damage of TAM in female rats. Rats received 45 mg/kg of TAM injections for 10 days, while the groups treated with CRDE received 12 ml/kg of CRDE for 20 days, commencing 10 days before TAM administration. TAM exposure resulted in apparent degenerations in hepatic tissue with inflammatory cell infiltration and loss of architectures. Serum levels of liver enzymes including alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were elevated, along with hepatic oxidative stress, as shown by increased lipid peroxidation with lower levels of reduced glutathione. TAM caused inflammation in the liver tissue as indicated by higher levels of tumor necrosis factor-α and interleukin-6 as well as increased expression of CD68; a phagocytic Kupffer's cells marker. Additionally, the protein expression analysis revealed a high expression of pyroptotic markers including NLRP3-inflammasome, caspase-1, and gasdermin D. Conversely, CRDE treatment effectively neutralized the biochemical, histological, and protein expression alterations induced by TAM. In conclusion, CRDE demonstrated the potential to protect the liver from TAM-induced damage by regulating mechanisms involving oxidative damage, inflammation, and pyroptosis. [ABSTRACT FROM AUTHOR]

The presence of arsenic (As) and fluoride (F−) in drinking water is of concern due to the enormous number of individuals exposed to this condition worldwide. Studies in cultured cells and animal models have shown that As- or F-induced hepatotoxicity is primarily associated with redox disturbance and altered mitochondrial homeostasis. To explore the hepatotoxic effects of chronic combined exposure to As and F− in drinking water, pregnant CD-1 mice were exposed to 2 mg/L As (sodium arsenite) and/or 25 mg/L F− (sodium fluoride). The male offspring continued the exposure treatment up to 30 (P30) or 90 (P90) postnatal days. GSH levels, cysteine synthesis enzyme activities, and cysteine transporter levels were investigated in liver homogenates, as well as the expression of biomarkers of ferroptosis and mitochondrial biogenesis-related proteins. Serum transaminase levels and Hematoxylin–Eosin and Masson trichrome-stained liver tissue slices were examined. Combined exposure at P30 significantly reduced GSH levels and the mitochondrial transcription factor A (TFAM) expression while increasing lipid peroxidation, free Fe 2+, p53 expression, and serum ALT activity. At P90, the upregulation of cysteine uptake and synthesis was associated with a recovery of GSH levels. Nevertheless, the downregulation of TFAM continued and was now associated with a downstream inhibition of the expression of MT-CO2 and reduced levels of mtDNA and fibrotic liver damage. Our experimental approach using human-relevant doses gives evidence of the increased risk for early liver damage associated with elevated levels of As and F− in the diet during intrauterine and postnatal period. [ABSTRACT FROM AUTHOR]

High temperatures cause abnormal energy metabolism and inhibit the growth of fish in aquaculture. However, the mechanism of energy metabolism under chronic heat stress is still unknown. In this study, largemouth bass (Micropterus salmoides, LMB) was treated with 25℃, 29℃, and 33℃ for 8 weeks. Then, the growth performance, liver tissue damage, serum lipid indicator, hepatic glycogen, and triglyceride levels were analyzed. The growth data showed that the 33℃ group had a lower weight gain rate (WGR), specific growth rate (SGR), feeding rate (FR), and higher feed conversion rate (FCR) in comparison with those in the 25℃ and 29℃ groups. However, there were no significant differences between the 25℃ and 29℃ groups. The most severe damage to liver tissue was observed in the 33℃ group, characterized by cellular vacuolation and marginalization of cell nuclei. The levels of triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol in the serum were decreased with the rising temperatures. However, the hepatic triglyceride levels were increased, with a decrease in hepatic glycogen levels. Compared with the 25℃ group, the expressions of gluconeogenesis pathway-related genes (phosphoenolpyruvate carboxykinase (Pepck) and glucose-6-phosphatase (G6pase)) and glucose transport pathway-related gene (glucose transporter 2 (Gltu2)) were down-regulated in the 33℃ group. In contrast, the expression of the glycolysis pathway-related gene (pyruvate kinase (Pk)) was up-regulated. In addition, the expressions of fatty acid β oxidation pathway-related genes (peroxisome proliferator-activated receptor-Alpha (Pparα) and carnitine palmityl transferase 1 (Cpt1)), adipogenesis pathway-related genes (peroxisome proliferator-activated receptor-Gamma (Pparγ), fatty acid synthase (Fas), acetyl-CoA carboxylase (Acc)), and lipolysis pathway-related genes (adipose triglyceride lipase (Agtl) and hormone-sensitive lipase (Hsl)) were down-regulated under chronic heat stress. In conclusion, our results indicated that enhancement of the glycolysis pathway and inhibition of the gluconeogenesis pathway and lipid metabolism contribute to coping with chronic heat stress for LMB. Our study provides useful information for alleviating the heat stress response of LMB through nutritional regulation in the future. [ABSTRACT FROM AUTHOR]

Background: Exposure to ionizing radiation is inevitable due to its extensive use in industrial and medical applications. The search for effective and safe natural therapeutic agents as alternatives to chemical drugs is crucial to mitigate their side effects. This study aimed to evaluate the effects of citicoline as a standalone treatment or in combination with the anti-hepatotoxic drug silymarin in protecting against liver injury caused by γ-radiation in rats. Methods and results: The rats were exposed to γ-radiation (7 Gy) and treated with citicoline (300 mg/kg/day) and/or silymarin (50 mg/kg/day). The results showed that citicoline alleviated liver damage in irradiated rats by reducing hepatic malondialdehyde levels, serum aspartate aminotransferase activity, and inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and nuclear factor-kappa B (NF-κB). It also increased acetylcholine (ACh) levels and the gene expression of the anti-inflammatory protein α7 nicotinic acetylcholine receptor (α7nAChR). Additionally, citicoline improved serum triiodothyronine (T3) levels, thyroid hormone receptor beta (TRβ) gene expression, and iodothyronine deiodinase type 1 activity in hepatic tissues of irradiated rats. Furthermore, citicoline enhanced the effects of silymarin on thyroxine (T4), TRβ, ACh, and α7nAChR when co-administered in irradiated rats. Histopathological analysis confirmed these findings, demonstrating improved liver tissue structure. Conclusions: Citicoline mitigates γ-radiation-induced liver damage by reducing oxidative stress, activating the cholinergic anti-inflammatory pathway, and modulating thyroid hormone metabolism. These findings support the use of citicoline as a safe standalone treatment or as an adjuvant with silymarin for managing liver damage and thyroid hormone disturbances caused by γ-irradiation. [ABSTRACT FROM AUTHOR]

Background/Objectives: The characterization of patients with inflammatory bowel disease (IBD) and type 2 diabetes mellitus (T2DM) as a new group has not been well detailed. This study aimed to evaluate the impact of T2DM on IBD progression and analyze the prevalence of steatotic liver disease and liver damage in these patients. Methods: Through a retrospective case–control study, we compared severe IBD occurrence in patients with both IBD-T2DM (cases) versus those with IBD alone (controls). Among 1047 medical records, 79 IBD-T2DM patients were selected and compared to 308 controls in a 1:4 ratio. Severe IBD was defined by variables such as surgery, target therapy, corticosteroid use, and hospitalization. Liver damage was assessed using Fib-4 (>1.3), and hepatic steatosis was evaluated by imaging. Results: There was no significant difference in severe disease rates (59.5% vs. 59.7%; p = 0.97). IBD-T2DM patients had higher rates of hepatic steatosis (62.9% vs. 27.2%; p < 0.0001) and liver damage (55.4% vs. 26.6%; p < 0.0001). IBD-T2DM patients used more corticosteroids (p < 0.0001) and fewer anti-TNF-alpha drugs (p = 0.007). The median age at diagnosis was higher in IBD-T2DM patients (48 vs. 32; p < 0.0001). In Crohn's disease, 24.3% of IBD-T2DM patients had exclusive colonic involvement compared to 5% in the IBD-only group (p = 0.003). Conclusions: T2DM was not associated with worse IBD progression, but was linked to increased liver steatosis and damage. Differences such as age of onset, colonic involvement, and liver damage suggest that IBD-T2DM patients could configure a special population worthy of further studies. [ABSTRACT FROM AUTHOR]

Fatty liver hemorrhagic syndrome (FLHS) in laying hens is a nutritional and metabolic disease involving liver enlargement, hepatic steatosis, and hepatic hemorrhage as the primary symptoms. The syndrome is prone to occur during the peak laying period of laying hens, which has resulted in significant economic losses in the laying hen breeding industry; however, the specific pathogenesis of FLHS remains unclear. Our group and previous studies have shown that bile acid levels are significantly decreased during the development of fatty liver and that targeted activation of bile acid–related signaling pathways is beneficial for preventing and treating fatty liver. In this study, we generated a FLHS laying hen model by feeding hens a high-energy, low-protein diet, with goose deoxycholic acid (CDCA) given as an intervention. HE staining, fluorescence quantitative PCR, and ELISA were used to evaluate the effects of CDCA on pathological changes and inflammatory responses in the liver. The results showed that hepatic hemorrhage in FLHS laying hens was reduced after CDCA treatment. Furthermore, fat vacuoles and transaminase levels decreased significantly. In addition, expression levels of M1-type macrophage markers and polarization products were significantly reduced, and the expression of pro-inflammatory regulatory factors related to the JAK-STAT signaling pathway, LPS-TLR4-Myd88–NF-kB signaling pathway, and NLRP3 inflammasomes decreased significantly as well. Expression levels of M2-type macrophage markers and polarization products increased significantly, as did the expression of anti-inflammatory regulators related to the JAK-STAT signaling pathway. These results suggest that CDCA ameliorates liver injury in laying hens with FLHS by inhibiting macrophage M1-type polarization and the resulting pro-inflammatory response, thereby promoting M2-type macrophage polarization and an anti-inflammatory response. [ABSTRACT FROM AUTHOR]

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Background/Objectives: Glecaprevir/pibrentasvir (G/P) and elbasvir/grazoprevir (EBR/GZR) are effective treatments for chronic hepatitis C (CHC), especially in patients with chronic kidney disease (CKD). However, both regimens carry a risk of drug-induced liver injury (DILI). This study investigates the association between renal failure and DILI, using real-world data, and assesses the effectiveness of these treatments in peritoneal dialysis patients. Methods: A retrospective cohort study was conducted using data from the Ditmanson Research Database, including patients with CHC treated with G/P or EBR/GZR from 1 August 2017 to 31 December 2020. Patients were categorized into CKD and normal kidney function (NKF) groups. Two sensitivity analyses were performed to assess DILI risk. The study was approved by the DMF-CYCH Institutional Review Board (CYCH IRB No.: 2021010). Results: In 837 patients, DILI risk, expressed as incidence rate ratios (IRR), was 0.64 (95% CI 0.25–1.63) in the NKF group and 1.29 (95% CI 0.12–14.23) in the CKD group. Sensitivity analyses showed consistent results. A case–time–control analysis suggested liver instability despite treatment, with comorbid liver tumors (aOR 18.89; 95% CI 5.4–66.12) and hypertension (aOR 4.25; 95% CI 1.49–12.15) linked to higher DILI risk. All peritoneal dialysis patients (n = 10) achieved a 100% SVR12 rate. Conclusions: This real-world study supports the effectiveness of G/P and EBR/GZR in peritoneal dialysis patients. Comorbidities that impair liver function are key predictors of abnormal liver parameters, highlighting the need for careful monitoring during CHC treatment. [ABSTRACT FROM AUTHOR]

Long-chain free fatty acids (FFAs) accumulation and oxidative toxicity is a major cause for several pathological conditions. The mechanisms underlying FFA cytotoxicity remain elusive. Here we show that palmitic acid (PA), the most abundant FFA in the circulation, induces S403 phosphorylation of SQSTM1/p62 (sequestosome 1) and its aggregation, which sequesters KEAP1 and activates the non-canonical SQSTM1-KEAP1-NFE2L2 antioxidant pathway. The PA-induced SQSTM1 S403 phosphorylation and aggregation are dependent on SQSTM1 K7-D69 hydrogen bond formation and dimerization in the Phox and Bem1 (PB1) domain, which facilitates the recruitment of TBK1 that phosphorylates SQSTM1 S403. The ubiquitin E3 ligase TRIM21 ubiquitinates SQSTM1 at the K7 residue and abolishes the PB1 dimerization, S403 phosphorylation, and SQSTM1 aggregation. TRIM21 is oxidized at C92, C111, and C114 to form disulfide bonds that lead to its oligomerization and decreased E3 activity. Mutagenizing the three C residues to S (3CS) abolishes TRIM21 oligomerization and increases its E3 activity. TRIM21 ablation leads to decreased SQSTM1 K7 ubiquitination, hence elevated SQSTM1 S403 phosphorylation and aggregation, which confers protection against PA-induced oxidative stress and cytotoxicity. Therefore, TRIM21 is a negative regulator of SQSTM1 phosphorylation, aggregation, and the antioxidant sequestration function. TRIM21 is oxidized to reduce its E3 activity that helps enhance the SQSTM1-KEAP1-NFE2L2 antioxidant pathway. Inhibition of TRIM21 May be a viable strategy to protect tissues from lipotoxicity resulting from long-chain FFAs. Abbreviations: ER: endoplasmic reticulum; FFA: free fatty acid; HMOX1/HO-1: heme oxygenase 1; IB: immunoblotting; IF: immunofluorescence; IP: immunoprecipitation; KEAP1: kelch like ECH associated protein 1; MASH: metabolic dysfunction-associated steatohepatitis; MEF: mouse embryonic fibroblast; NFE2L2/Nrf2: NFE2 like BZIP transcription factor 2; PA: palmitic acid; PB1: Phox and Bem 1; ROS: reactive oxygen species; SLD: steatotic liver disease; SQSTM1: sequestosome 1; TBK1: TANK-binding kinase 1; TRIM21: tripartite motif containing 21. [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]

Aflatoxin B1 (AFB1) is a prevalent contaminant in food and feed matrices, known for its hepatotoxic effects. Its metabolic breakdown generates reactive oxygen species (ROS), leading to oxidative stress and subsequent liver damage. Mitigating oxidative stress is, therefore, essential for ameliorating the hepatocellular damage and systemic toxicity caused by AFB1. Here, we synthesized arginine carbon dots (Arg-CDs) with robust antioxidant properties through a simple hydrothermal method using arginine and citric acid. Our investigation demonstrated that Arg-CDs effectively mitigate oxidative stress in nematodes. Furthermore, in murine models of AFB1-induced hepatic injury, Arg-CDs effectively restored liver function, as evidenced by the improvement in histopathological features and biochemical markers. Notably, Arg-CDs administration upregulated the transcriptional activity of nuclear factor erythroid 2-related factor 2 (Nrf2), along with its downstream antioxidant effectors and phase II detoxifying enzymes under AFB1 exposure. Moreover, Arg-CDs alleviated hepatic inflammatory injury by modulating the NLRP3/Caspase-1/GSDMD-mediated pyroptosis pathway. Arg-CDs also demonstrated therapeutic potential in enhancing intestinal barrier function in AFB1-exposed mice. Collectively, these findings highlight the potential of Arg-CDs as a novel and biocompatible therapeutic modality for alleviating AFB1-induced hepatic and intestinal damage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

Crimean-Congo hemorrhagic fever virus (CCHFV) is a member of the family Nairoviridae in the Hareavirales order and is an important human pathogen. Hepatic injury is a salient feature of CCHF human disease and can be recapitulated in murine models. Here, we described techniques to study liver damage caused by CCHFV in the mouse system. These techniques include a description of the mouse model used to study disease, and classical histopathological methods. Additionally, the use of in situ hybridization to evaluate liver injury is described in the context of viral infection. Immunofluorescence staining techniques to identify infected and/or damaged Kupffer cells is also explained. This work provides a primer for the comprehensive pathophysiological study of liver infection by a virus, but also has utility for noninfectious liver injury as well., (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)