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Metabolic dysfunction-associated fatty liver disease (MASLD), a persistent liver condition associated with metabolic syndrome, is primarily caused by excessive fructose intake and a typical Western diet. Because there is currently only one approved treatment, lifestyle and dietary interventions are crucial. This study assessed the effects of dietary intervention involving freeze-dried plum (FDP), a natural source of antioxidants containing diverse polyphenols. This study aimed to assess its potential as a protective agent against the gut–liver axis and its therapeutic effects on liver injury and gut permeability issues associated with MASLD. We indicate that 10% FDP intake restored gut barrier proteins and reduced serum endotoxin levels in the MASLD mouse models. Additionally, 10% FDP intake significantly reduced hepatic oxidative stress, lipid metabolism, and fibrosis marker levels. Interestingly, FDP intake significantly reduced the levels of inflammatory cytokine tumor necrosis factor-α and markers of liver damage, such as serum alanine aminotransferase/aspartate aminotransferase and hepatic triglycerides. These results highlight that dietary intervention with FDP that acts as a natural antioxidant may be a significant protective and therapeutic agent against liver and gut damage caused by MASLD. [ABSTRACT FROM AUTHOR]

Alhagi-honey (AH) is a well-established traditional ethnic medicine with advantageous effects against diarrhea and headaches. We aimed to explore the preventive effect of AH on liver damage induced by heat stress (HS) and its underlying mechanism. HS models were established by thermostat, and mice were treated at 39 ℃ for 10 h, lasting for 7 days. Hematoxylin–eosin (H&E) staining and Periodic Acid-Schiff (PAS) staining were used for histological observation, and transmission electron microscopy (TEM) was used for ultrastructure examination of hepatocytes. Gut microbiota (GM) composition and liver metabolites were respectively analyzed by 16S rRNA sequencing and non-targeted metabolome sequencing. AH pretreatment alleviated liver damage caused by heat stress in mice. The main manifestation was that AH alleviated serum aspartate transferase (AST) and aspartate transaminase (ALT). It was found that AH improved symptoms of hepatocyte damage. In addition, the relative abundance of f_Rikenellaceae, g_Incertae_Sedis and s_Staphylococcus_Orisratti, g_Lachnoclostridium, g_GCA-900066575, and s_Alistipes_inops were modified by AH and these bacterial genera showed association with 6 metabolites (2- (3,4-dihydroxyphenyl) acetamide, 3-hydroxy-3-methylpentanedioic acid, PC (17:0/17:1), Y-L-Glutamy-L-glutamic acid, L-Isoleucine, 5-Methyluridine, 8,8-dimethyl-2-phenyl-4H,8H-pyrano [2, 3-h] chromen-4-one). The Pearson analysis also showed a strong correlation between these microbes and 2 risk indicators (AST and ALT) of liver damage. AH alleviated HS-induced liver damage by regulating liver metabolism and maintaining normal GM. It demonstrated that AH held potential as a prophylactic drug for the prevention of HS-induced liver damage. Highlights: AH can prevent heat stress-induced liver damage. AH regulated gut bacterial abundance to promote the production of beneficial metabolites. AH can prevent heat stress-induced liver damage and its complications as a dietary additive/natural medicine. [ABSTRACT FROM AUTHOR]

This study investigated the protective effects of chlorogenic acid (CGA) on production performance and liver function of rabbits under heat stress (HS) condition. A total of 120 healthy New Zealand weaned rabbits with similar initial body weight, were randomly divided into 3 treatments with 20 replicates per treatment and 2 weaned rabbits per replicate: control (CON) group (rabbits were housed at 25 ± 1°C and fed a basal diet), HS group (rabbits were housed at 35 ± 1°C and fed a basal diet), and HS + CGA group (rabbits were housed at 35 ± 1°C and fed a basal diet supplemented with 800 mg/kg CGA). The trial lasted for 28 days. The results showed that HS challenge decreased (p < 0.05) growth performance, induced oxidative stress and hepatic apoptosis, and caused liver damage in rabbits. However, dietary CGA supplementation increased (p < 0.05) body weight gain and feed efficiency, and enhanced (p < 0.05) antioxidative capacity in serum and liver in HS‐challenged rabbits; attenuated HS‐induced increases in urea nitrogen (p = 0.03), alanine aminotransferase (p = 0.03), aspartate aminotransferase (p = 0.01), caspase‐8 (p = 0.02), and caspase‐3 (p = 0.04) as well as decrease albumin (p = 0.04). Moreover, supplementation with CGA upregulated Nrf2/HO‐1 pathway‐related genes expressions, including Nrf2 (p = 0.009), HO‐1 (p = 0.03) and SOD1 (p = 0.04) in HS‐challenged rabbits. Our findings demonstrated that dietary CGA supplementation could alleviate HS‐induced decline in growth performance, and protect against HS‐induced liver damage partially through enhancing antioxidant capacity via acting Nrf2/HO‐1 pathway and inhibiting hepatic apoptosis in rabbits. [ABSTRACT FROM AUTHOR]

Background: Thalassemia is a hemoglobin synthesis disorder that causes patients to need lifelong blood transfusions, leading to iron overload and alter organ function, including the liver. Hepcidin, produced by the liver, plays a role in iron homeostasis and should be increased in excess iron stores. However, the level decreases in thalassemia due to some factors, such as ineffective erythropoiesis and liver damage. Recent publications revealed that hepcidin could be associated with iron overload and also a marker of liver diseases. Objective: To analyse the correlation between hepcidin level, markers of iron overload, and liver damage in β-thalassemia major. Methods: This cross-sectional study included all β-thalassemia major age 2-18 years admitted to Dr. Mohammad Hoesin Hospital, Palembang, South Sumatera, who underwent blood transfusions from March to August 2022. We measured the level of iron overload markers, hepcidin, liver function test (LFT), and performed liver ultrasonography (USG). Results: Of 97 subjects, median hepcidin level was 10.01 ng/mL and 68% of the subjects showed a decrease. The iron overload parameters were evaluated from serum iron levels (P=0.13), ferritin levels (P=0.90), and transferrin saturation (P=0.29) and 24.7% had abnormal liver USG findings. Spearman's correlation revealed that only direct bilirubin (DB) (r=0.35; P=0.001) and liver USG (r=0.20; P=0.05) had positive correlations with decreased levels of hepcidin. Also, it had 91.7% sensitivity in predicting liver damage from ultrasound. Conclusion: The hepcidin level was not significantly associated with iron overload markers. [ABSTRACT FROM AUTHOR]

Microcystin-LR (MC-LR), frequently generated by cyanobacteria, has been demonstrated to raise the likelihood of liver disease. Few previous studies have explored the potential antagonist against MC-LR. Astaxanthin (ASX) has been shown to possess various beneficial effects in regulating lipid metabolism in the liver. However, whether ASX could alleviate MC-LR-induced hepatic lipid metabolic dysregulation is as yet unclear. In this work, the important roles and mechanisms of ASX in countering MC-LR-induced liver damage and lipid metabolic dysregulation were explored for the first time. The findings revealed that ASX not only prevented weight loss but also enhanced liver health after MC-LR exposure. Moreover, ASX effectively decreased triglyceride, total cholesterol, aspartate transaminase, and alanine aminotransferase contents in mice that were elevated by MC-LR. Histological observation showed that ASX significantly alleviated lipid accumulation and inflammation induced by MC-LR. Mechanically, ASX could significantly diminish the expression of genes responsible for lipid generation (Srebp-1c, Fasn, Cd36, Scd1, Dgat1, and Pparg), which probably reduced lipid accumulation induced by MC-LR. Analogously, MC-LR increased intracellular lipid deposition in THLE-3 cells, while ASX decreased these symptoms by down-regulating the expression of key genes in the lipid synthesis pathway. Our results implied that ASX played a crucial part in lipid synthesis and effectively alleviated MC-LR-induced lipid metabolism dysregulation. ASX might be developed as a novel protectant against hepatic impairment and lipid metabolic dysregulation associated with MC-LR. This study offers new insights for further management of MC-LR-related metabolic diseases. [ABSTRACT FROM AUTHOR]

In recent years, the environmental pollution caused by microplastics (MPs) has attracted extensive attention. Numerous studies have shown that MPs could cause liver damage in aquatic animals. However, there is a limited range of technical approaches available to mitigate and minimize the detrimental impact of MPs on both wild fish populations and aquaculture operations. Thus, this study aimed to investigate the impact of dietary chitosan supplementation on the prevention and treatment of liver damage induced by exposure to polystyrene microplastics (PS-MPs) in Nile tilapia (Oreochromisniloticus). The results indicated that after two weeks of exposure, the liver of tilapia showed oxidative stress, inflammatory response and fibrosis. Meanwhile, after the chitosan addition, the oxidative stress, inflammatory response and fibrosis of tilapia liver were reversed, the pyroptosis and ferroptosis in tilapia liver were inhibited, the combination of mitochondria with PS-MPs in tilapia liver cells was inhibited, and the mitochondrial damage was reversed. In summary, the study confirmed the potential prophylaxis and treatment effect of dietary chitosan supplementation on PS-MPs exposure-induced liver damage in tilapia, and provided basic data for further studies on prophylaxis and treatment of the toxic effects of MPs. This study also presented efficacious strategies for alleviating the deleterious impacts of MPs on fish farming, thereby fostering sustainable and eco-friendly approaches in aquaculture. [ABSTRACT FROM AUTHOR]

Topiramate (TPM), a carbonic anhydrase (CA) inhibitor, is known for its anti-obesity effect. Even though, nonalcoholic fatty liver disease (NAFLD) is present in 80% of obese patients, TPM's effects on oxidant-antioxidant parameters and CA activity on fatty liver is not known. 24 Wistar albino rats were divided into four groups: control, TPM, diet, and diet + TPM. Diet groups fed with high-fat diet while control and TPM groups received standard chow for six weeks. Than 100 mg/kg/day TPM (po) was added to TPM groups for 21 days. Rats' weight and blood glucose levels were monitored weekly, and at the end of the study liver removed for biochemical and histological analysis. TPM eliminated the increases in weight and blood glucose levels caused by high-fat diet. TPM decreased CA activity in all groups. MDA levels increased significantly in TPM and DT groups (p = 0.004; p = 0.008). GSH levels were decreased in the TPM, D and DT groups (p = 0.004; p = 0.015; p = 0.003). Similarly, GPx activity levels were significantly decreased in all groups. Histological evaluation revealed notable infiltration, eosinophilia and cytoplasmic vacuolization in the TPM group. Steatosis and NAFLD activity score (NAS) were higher in the diet group. Ballooning, infiltration and NAS were higher in the diet + TPM group compared to control. CA activity negatively correlated with MDA (p < 0.001), and positively correlated with GSH (p < 0.001). TPM caused oxidant stress and liver damage, which are exacerbated in NAFLD induced rats. Therefore, use of TPM in patients with liver disease should be considered very carefully. [ABSTRACT FROM AUTHOR]

Chronic arsenic poisoning is a public health problem worldwide. In addition to skin lesions, the detrimental effect of arsenic poisoning on liver damage is one of the major issues. Our previous studies demonstrated that endoplasmic reticulum (ER) stress and p53 were associated with arsenic-induced liver damage. Literature has shown that EI24 is involved in hepatocyte hypertrophy; however, the underlying role and mechanism in arsenic-induced liver damage have not been fully elucidated. In this study, we explored the role of ER stress, p53, and EI24 as well as the regulatory relationship in arsenic poisoning populations and L-02 cells treated with distinct concentration NaAsO2 (2.5, 5, 10, and 20 μM). Results showed that as with arsenic dose increment, expression levels of ER stress key proteins GRP78, ATF4, and CHOP were significantly enhanced. Additionally, p53 expression in nucleus, p53 phosphorylation at Ser15 and Ser1392, and p53 acetylation at lys382 were significantly increased in NaAsO2-treated L-02 cells. ER stress inhibitor 4-phenylbutyric acid (4-PBA) decreased the expression of p53 phosphorylation at Ser 392, p53 acetylation at lys382, and p53 expression in nucleus. Additionally, in 5 μM NaAsO2 condition, p53 inhibitor pifithrin-α (PFT-α) aggravated 5 μM NaAsO2-induced GRP78, ATF4, and CHOP expressions, cell apoptosis, and protein-SH consumption. But in 20 μM NaAsO2 condition, PFT-α attenuated NaAsO2-induced cell apoptosis. Further results showed that 20 μM NaAsO2 facilitated translocation of EI24 from ER to mitochondrion and interaction with VDAC2, leading to activate mitochondrial apoptotic pathway, but not observed in the 5-μM NaAsO2 group. Moreover, PFT-α and 4-PBA inhibited 20 μM NaAsO2-induced EI24 expression in mitochondrion. Collectively, our results indicated that arsenic induced p53 activation via ER stress, under relatively low NaAsO2 concentration, NaAsO2-triggered p53 activation protected cells from apoptosis by alleviating ER stress. Another finding was that under relatively high NaAsO2 concentration, NaAsO2-activated p53 facilitated EI24 mitochondrial translocation and caused mitochondrial permeability increase, which represented a switch of p53 from a benefit role to pro-apoptosis function in NaAsO2-treated cells. The study contributed to in-depth understanding the mechanism of arsenic-induced liver damage and providing potential clues for following study. [ABSTRACT FROM AUTHOR]

Intravascular hemolysis is a central feature of congenital and acquired hemolytic anemias, complement disorders, infectious diseases, and toxemias. Massive and/or chronic hemolysis is followed by the induction of inflammation, very often with severe damage of organs, which enhances the morbidity and mortality of hemolytic diseases. Galectin-3 (Gal-3) is a β-galactoside-binding lectin that modulates the functions of many immune cells, thus affecting inflammatory processes. Gal-3 is also one of the main regulators of fibrosis. The role of Gal-3 in the development of different kidney and liver diseases and the potential of therapeutic Gal-3 inhibition have been demonstrated. Therefore, the objective of this review is to discuss the possible effects of Gal-3 on the process of kidney and liver damage induced by intravascular hemolysis, as well as to shed light on the potential therapeutic targeting of Gal-3 in intravascular hemolysis. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) remains a public health concern. Blood donors screened for HBV surface antigen (HBsAg) along with aspartate transaminase (AST)/alanine aminotransferase (ALT) could play a key in providing safe blood products. We investigated the features related to HBV infection among rejected blood donors in Luanda, Angola. Methods: This was a cross‐sectional study conducted with 164 rejected donors. Donors were screened for HBsAg from March to May 2022. Overall, 63.4% tested positive for HBV. Results: The mean age of the HBV‐positive (29.2 ± 8.02) was lower than the HBV‐negative (33.9 ± 10.0) (p < 0.001). Donors between 20 and 40 years (odds ratio [OR]: 2.34, p = 0.045), females (OR: 1.40, p = 0.516), residents in urbanized areas (OR: 1.23, p = 0.530), low educational (OR: 1.54, p = 0.458), unemployed (OR: 1.65, p = 0.271), and unmarried (OR:1.41, p = 0.616) might be likely to contract HBV. AST/ALT ratio was higher in HBV‐infected (2.07 ± 1.42) than in HBV‐uninfected (1.90 ± 1.14). About 20% of HBV‐positive were classified as having acute liver disease, while 80% with chronic liver disease, based on AST/ALT ratio. Age ranged from 20 to 40 years (OR: 1.97, p = 0.305), females (OR: 1.61, p = 0.557), donors from non‐urbanized (OR: 1.69, p = 0.557), a low educational (OR: 1.64, p = 0.571), and unemployed donors (OR: 1.81, p = 0.289) were likely to develop chronic liver disease. Conclusions: Our findings indicated the failure of viral hepatitis control measures. Authorities should consider including HBV nucleic acid testing to ensure early identification of HBV in Angola. [ABSTRACT FROM AUTHOR]

Liver fibrosis is the consequence of chronic liver injury in the presence of an inflammatory component. Although the main executors of this activation are known, the mechanisms that lead to the inflammatory process that mediates the production of pro‐fibrotic factors are not well characterized. Epidermal growth factor receptor (EGFR) signaling in hepatocytes is essential for the regenerative processes of the liver; however, its potential role in regulating the fibrotic niche is not yet clear. Our group generated a mouse model that expresses an inactive truncated form of the EGFR specifically in hepatocytes (ΔEGFR mice). Here, we have analyzed the response of WT and ΔEGFR mice to chronic treatment with carbon tetrachloride (CCl4), which induces a pro‐inflammatory and fibrotic process in the liver. The results indicated that the hallmarks of liver fibrosis were attenuated in CCl4‐treated ΔEGFR mice when compared with CCl4‐treated WT mice, coinciding with a faster resolution of the fibrotic process and ameliorated damage. The absence of EGFR activity in hepatocytes induced changes in the pattern of immune cells in the liver, with a notable increase in the population of M2 macrophages, more related to fibrosis resolution, as well as in the population of lymphocytes related to eradication of the damage. Transcriptome analysis of hepatocytes, and secretome studies of extracellular media from in vitro experiments, allowed us to elucidate the specific molecular mechanisms regulated by EGFR that mediate hepatocyte production of both pro‐fibrotic and pro‐inflammatory mediators; these have consequences for the deposition of extracellular matrix proteins, as well as for the immune microenvironment. Overall, our study uncovered novel mechanistic insights regarding EGFR kinase‐dependent actions in hepatocytes that reveal its key role in chronic liver damage. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Modulators of cystic fibrosis transmembrane conductance regulator (CFTR) improved cystic fibrosis (CF) patients' outcome. The elexacaftor/tezacaftor/ivacaftor (ETI) combination was safe and effective improving lung function in patients with different CFTR genotypes, including at least one F508del mutation. However, cases with liver damage were reported. We describe 105 CF patients heterozygous for F508del in trans with another CFTR mutation, treated for 1 year with ETI. We analyzed liver biochemical parameters and cholesterol metabolism, including lathosterol and phytosterols, surrogate markers of cholesterol de-novo synthesis and absorption, respectively. The treatment significantly improved sweat chloride, body mass index and forced expiratory volume in 1 s, whereas it caused a significant increase of total and conjugated bilirubin, ALT and GGT, even if no patients developed CF liver disease. Such alterations were less relevant than those previously observed in ETI-treated F508del homozygous patients. Furthermore, ETI treatment significantly increased serum cholesterol by enhancing its absorption (correlation between serum cholesterol and phytosterols). Whereas, we observed a normalization of de-novo biosynthesis (lathosterol reduction) that was not observed in homozygous patients. These data suggest that the second mutation in trans with the F508del contributes to reduce the liver cholesterol accumulation and thus, the triggering of liver inflammation. However, no differences in the alteration of biochemical indexes were observed between CF patients with and without liver steatosis, and between patients with different mutations in trans with the F508del. Such data suggest to further investigate the effects of ETI therapy on liver function indexes and new predictive biomarkers. [ABSTRACT FROM AUTHOR]

Background: Secondary carnitine deficiency in patients with anorexia nervosa has been rarely reported. This study aimed to investigate the occurrence of carnitine deficiency in severely malnourished patients with eating disorders during refeeding and assess its potential adverse effects on treatment outcomes. Method: In a cohort study of 56 female inpatients with eating disorders at a single hospital from March 2010 to December 2020, we measured plasma free carnitine (FC) levels and compared to those of a healthy control group (n = 35). The patients were categorized into three groups based on FC levels: FC deficiency (FC< 20 µmol/L), FC pre-deficiency (20 µmol/L ≤ FC< 36 µmol/L), and FC normal (36 µmol/L ≤ FC). Results: Upon admission, the patients had a median age of 26 years (interquartile range [IQR]: 21–35) and a median body mass index (BMI) of 13.8 kg/m2 (IQR: 12.8–14.8). Carnitine deficiency or pre-deficiency was identified in 57% of the patients. Hypocarnitinemia was associated with a decline in hemoglobin levels during refeeding (odds ratio [OR]: 0.445; 95% confidence interval [CI]: 0.214–0.926, p = 0.03), BMI at admission (OR: 0.478; 95% CI: 0.217–0.874, p = 0.014), and moderate or greater hepatic impairment at admission (OR: 6.385; 95% CI: 1.170–40.833, p = 0.032). Conclusions: Hypocarnitinemia, particularly in cases of severe undernutrition (BMI< 13 kg/m2 at admission) was observed in severely malnourished patients with eating disorders during refeeding, a critical metabolic transition phase. Moderate or severe hepatic impairment at admission was considered a potential indicator of hypocarnitinemia. Although hypocarnitinemia was not associated with any apparent adverse events other than anemia during refeeding, the possibility that carnitine deficiency may be a risk factor for more serious complications during sudden increases in energy requirements associated with changes in physical status cannot be denied. Further research on the clinical significance of hypocarnitinemia in severely malnourished patients with eating disorders is warranted. Plain English summary: Carnitine is an amino acid derivative that plays an important role in the promotion and regulation of fatty acid metabolism, and carnitine deficiency is assumed in patients with anorexia nervosa associated with chronic starvation, but there are few reports on this issue. This study represents the inaugural documentation of hypocarnitinemia in severely malnourished patients with eating disorders, including anorexia nervosa. Hypocarnitinemia, particularly in cases of severe undernutrition (BMI < 13 kg/m2) was observed during refeeding, a critical metabolic transition phase. Moderate or severe hepatic impairment was considered a potential indicator of hypocarnitinemia. Although no apparent association with adverse events other than anemia during refeeding was identified, clinical manifestations of hypocarnitinemia may occur when a sudden increase in energy demand is added to a change in the physical condition of the patient group. Further investigation is required to determine the clinical significance of hypocarnitinemia. [ABSTRACT FROM AUTHOR]

For this study, 240 adult healthy female zebrafish were divided into 12 tanks (20 fish per tank) and exposed to 0 (control, T0), 0.1 (T1), 1 (T2), and 10 (T3) mg/L synthesized polystyrene nanoplastics (PS-NPs, nanoplastics synthesized in the chemistry laboratory of the Faculty of Basic Sciences at Zabol University) for 4 weeks. At the end of the experiment, exposure to PS-NPs had no significant effect on the survival of female zebrafish (P>0.05). A significant decrease of hepatic vitellogenin (Vtg) was seen in female zebrafish exposed to PS-NPs (P<0.05). The level of 17-β-estradiol (E2) and testosterone (T) were notably declined in female zebrafish of all PS-NPs-exposed groups (P<0.05). Glucose was notably increased in female zebrafish of all PS-NPs-exposed treatments (P<0.05). There was a significant increase in cortisol levels in all PS-NPs-exposed treatments (P<0.05). No significant difference was seen in lactate levels between different treatments (P>0.05). A significant enhancement in aspartate aminotransferase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) was observed in female zebrafish of all PS-NPs-exposed treatments compared to the control (P<0.05). The present results demonstrate that PS-NPs impair the reproduction process so that none of the female zebrafish broodstock exposed to different doses of PS-NPs reached the spawning stage. [ABSTRACT FROM AUTHOR]

The development of alcohol-associated liver disease (ALD) is associated with disorganized Golgi apparatus and accelerated phagophore formation. While Golgi membranes may contribute to phagophores, association between Golgi alterations and macroautophagy/autophagy remains unclear. GOLGA4/p230 (golgin A4), a dimeric Golgi matrix protein, participates in phagophore formation, but the underlying mechanism is elusive. Our prior research identified ethanol (EtOH)-induced Golgi scattering, disrupting intra-Golgi trafficking and depleting RAB3D GTPase from the trans-Golgi. Employing various techniques, we analyzed diverse cellular and animal models representing chronic and chronic/binge alcohol consumption. In trans-Golgi of non-treated hepatocytes, we found a triple complex formed between RAB3D, GOLGA4, and MYH10/NMIIB (myosin, heavy polypeptide 10, non-muscle). However, EtOH-induced RAB3D downregulation led to MYH10 segregation from the Golgi, accompanied by Golgi fragmentation and tethering of the MYH10 isoform, MYH9/NMIIA, to dispersed Golgi membranes. EtOH-activated autophagic flux is evident through increased WIPI2 recruitment to the Golgi, phagophore formation, enhanced LC3B lipidation, and reduced SQSTM1/p62. Although GOLGA4 dimerization and intra-Golgi localization are unaffected, loss of RAB3D leads to an extension of the cytoplasmic N terminal domain of GOLGA4, forming GOLGA4-positive phagophores. Autophagy inhibition by hydroxychloroquine (HCQ) prevents alcohol-mediated Golgi disorganization, restores distribution of ASGR (asialoglycoprotein receptor), and mitigates COL (collagen) deposition and steatosis. In contrast to short-term exposure to HCQ, extended co-treatment with both EtOH and HCQ results in the depletion of LC3B protein via proteasomal degradation. Thus, (a) RAB3D deficiency and GOLGA4 conformational changes are pivotal in MYH9-driven, EtOH-mediated Golgiphagy, and (b) HCQ treatment holds promise as a therapeutic approach for alcohol-induced liver injury. Abbreviation: ACTB: actin, beta; ALD: alcohol-associated liver disease; ASGR: asialoglycoprotein receptor; AV: autophagic vacuoles; EM: electron microscopy; ER: endoplasmic reticulum; EtOH: ethanol; HCQ: hydroxychloroquine; IP: immunoprecipitation; KD: knockdown; KO: knockout; MYH10/NMIIB: myosin, heavy polypeptide 10, non-muscle; MYH9/NMIIA: myosin, heavy polypeptide 9, non-muscle; PLA: proximity ligation assay; ORO: Oil Red O staining; PM: plasma membrane; TGN: trans-Golgi network; SIM: structured illumination super-resolution microscopy. [ABSTRACT FROM AUTHOR]

Maturity Onset Diabetes of the Young (MODY) is an autosomal dominant inherited disorder prevalent among adolescents. Typically, it manifests with hyperglycemia before the age of 25. MODY5 is attributed to a mutation in the Hepatocyte Nuclear Factor-1β (HNF-1β) gene. A complete absence of HNF-1β is observed in 50% of those with MODY5. The 17q12 microdeletion syndrome closely linked with MODY5. Its incidence in the general population is around 1 in 14,500 and is linked with facial deformities, diabetes, polycystic kidneys, pancreatic hypertrophy, liver anomalies, and neuropsychological impairments. The most primary clinical signs are predominantly associated with the HNF-1β gene deletion. We chronicle the case of a male of 19 years of age diagnosed with diabetes, who, alongside persistent liver damage and polycystic kidneys, was referred from a community hospital to the Xuzhou Central Hospital. His clinical presentation included diabetes, liver dysfunction, polycystic kidneys, lipid irregularities, insulin resistance, and fatty atrophy. Subsequent genetic screening unveiled a 17q12 chromosomal deletion and an absence of the Hepatocyte Nuclear Factor-1β (HNF-1β) gene. Hence, for adolescent patients lacking a familial diabetes history but exhibiting symptoms like polycystic kidneys, liver damage, lipid irregularities, and fatty atrophy, a thorough assessment for the 17q12 microdeletion syndrome becomes imperative. [ABSTRACT FROM AUTHOR]

Long-term exposure to amiodarone, an antiarrhythmic drug, can induce different organ damage, including liver. Cell damage included by amiodarone is a consequence of mitochondrial damage, reactive oxygen species production, and cell energy depletion leading to programmed cell death. In the present study, hepatoprotective potential of neurohormone melatonin (50 mg/kg/day) was evaluated in a chronic experimental model of liver damage induced by a 4-week application of amiodarone (70 mg/kg/day). The obtained results indicate that amiodarone induces an increase in xanthine oxidase activity, as well as the content of the lipid and protein oxidatively modified products and p53 levels. Microscopic analysis further corroborated the biochemical findings revealing hepatocyte degeneration, apoptosis, and occasional necrosis, with the activation of Kupffer cells. Coadministration of melatonin and amiodaron prevented an increase in certain damage associated parameters, due to its multiple targets. In conclusion, the application of melatonin together with amiodarone prevented an increase in tissue oxidative damage parameters and moderately prevented liver cell apoptosis, indicating that the damage of hepatocytes provoked by amiodarone supersedes the protective properties of melatonin in a given dose. [ABSTRACT FROM AUTHOR]

The primary purpose of this study was to evaluate the significance level between the liver damage marker (ALT-AST) levels taken in both periods from individuals who came to Ardahan State Hospital before and after the coronavirus disease of 2019 (COVID-19) disease period that appeared in our country in March 2020. Patients with chronic viral infections, alcohol use problems, liver cancer, chronic liver disease and cirrhosis were excluded from the study. Considering the period of March 2020, which was the first time it was seen in our country, liver marker levels of the same patients were examined in both periods, before and after. Statistical significance levels were evaluated and discussed in the literature. It was determined that 68 of 96 individuals (70.8%), whose ALT and AST enzyme levels were examined before and after COVID-19, had an increase in ALT and AST levels compared with the pre-COVID-19 period. The COVID-19 pandemic, a new era in human life, continues even though it has lost its effect. These effects include the stress of the illness period, the side effects of the medications used and the permanent damage caused by the COVID-19 infection. Because of these results, liver checquese and orientation towards a healthy life are of great importance after the COVID-19 period. [ABSTRACT FROM AUTHOR]

A 53-year-old woman was diagnosed with liver dysfunction in August 20XX. Computed tomography (CT) revealed multiple hepatic AV shunts, and she was placed under observation. In March 20XX + 3, she developed back pain, and CT performed during an emergency hospital visit showed evidence of intrahepatic bile duct dilatation. She was referred to our gastroenterology department in May 20XX + 3. We conducted investigations on suspicion of hereditary hemorrhagic telangiectasia (HHT) with hepatic AV shunting based on contrast-enhanced CT performed at another hospital. HHT is generally discovered due to epistaxis, but there are also cases where it is diagnosed during examination of liver damage. [ABSTRACT FROM AUTHOR]

Asparagus racemosus Willd., Cajanus cajan (L.) Millsp., Cassia fistula L., and Carissa spinarum L. (ACCC) are used in ethnomedicine for treating a variety of diseases, including liver disease. The present study investigated the combined antioxidative and hepatoprotective roles of an aqueous methanol extract of ACCC (AMACCC) on CCl4 -induced hepatic damage in the rat model. Thirty male Wistar Albino rats were divided uniformly into five groups. Group I (control) received only the vehicle DMSO (0.5 mL/kg b.w.) and was fed a normal diet for 28 days. Carbon tetrachloride (0.5 mL/kg b.w., 20% CCl4 /olive oil) was used to intoxicate groups II-V. Rats in Group II remained untreated, while groups III, IV, and V were given 50 mg/kg b.w. of sylimarin, 100 mg/kg b.w., and 200 mg/kg b.w. of AMACCC, respectively, for 28 days. Investigations were conducted to evaluate the combined action of AMACCC on liver marker enzymes along with histopathological changes of hepatic tissue before and after treatment. In vitro antioxidative activity of AMACCC was also observed. There were significant increases (p<0.001) in serum hepatic enzyme markers (ALT, AST, and ALP) activities in rats intoxicated with CCl4 when compared to the normal group, but administration of AMACCC extract at doses of 100 mg/kg and 200 mg/kg body weight and standard sylimarin drug attenuated (p<0.01) the toxic effects of CCl4 . The treated liver was shown to be in repair histopathologically. The combination of the four plant extracts has a strong hepatoprotective effect, indicating that more research is needed. [ABSTRACT FROM AUTHOR]

Iridovirus poses a substantial threat to global aquaculture due to its high mortality rate; however, the molecular mechanisms underpinning its pathogenesis are not well elucidated. Here, a multi-omics approach was applied to groupers infected with Singapore grouper iridovirus (SGIV), focusing on the roles of key metabolites. Results showed that SGIV induced obvious histopathological damage and changes in metabolic enzymes within the liver. Furthermore, SGIV significantly reduced the contents of lipid droplets, triglycerides, cholesterol, and lipoproteins. Metabolomic analysis indicated that the altered metabolites were enriched in 19 pathways, with a notable down-regulation of lipid metabolites such as glycerophosphates and alpha-linolenic acid (ALA), consistent with disturbed lipid homeostasis in the liver. Integration of transcriptomic and metabolomic data revealed that the top enriched pathways were related to cell growth and death and nucleotide, carbohydrate, amino acid, and lipid metabolism, supporting the conclusion that SGIV infection induced liver metabolic reprogramming. Further integrative transcriptomic and proteomic analysis indicated that SGIV infection activated crucial molecular events in a phagosome-immune depression-metabolism dysregulation-necrosis signaling cascade. Of note, integrative multi-omics analysis demonstrated the consumption of ALA and linoleic acid (LA) metabolites, and the accumulation of L-glutamic acid (GA), accompanied by alterations in immune, inflammation, and cell death-related genes. Further experimental data showed that ALA, but not GA, suppressed SGIV replication by activating antioxidant and anti-inflammatory responses in the host. Collectively, these findings provide a comprehensive resource for understanding host response dynamics during fish iridovirus infection and highlight the antiviral potential of ALA in the prevention and treatment of iridoviral diseases. [ABSTRACT FROM AUTHOR]

The complex epidemiology of hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV) patients in West Mexico remains poorly understood. Thus, this study aimed to investigate the HCV prevalence, HCV-associated risk factors, and HCV genotypes/subtypes and assess their impacts on liver fibrosis in 294 HIV patients (median age: 38 years; 88.1% male). HCV RNA was extracted and amplified by PCR. Hepatic fibrosis was assessed using three noninvasive methods: transient elastography (TE), the aspartate aminotransferase (AST)-to-platelets ratio index score (APRI), and the fibrosis-4 score (FIB4). Patients with liver stiffness of ≥9.3 Kpa were considered to have advanced liver fibrosis. HCV genotypes/subtypes were determined by line probe assay (LiPA) or Sanger sequencing. The prevalence of HIV/HCV infection was 36.4% and was associated with injection drug use (odds ratio (OR) = 13.2; 95% confidence interval (CI) = 5.9–33.6; p < 0.001), imprisonment (OR = 3.0; 95% CI = 1.7–5.4; p < 0.001), the onset of sexual life (OR = 2.6; 95% CI = 1.5–4.5; p < 0.001), blood transfusion (OR = 2.5; 95% CI = 1.5–4.2; p = 0.001), tattooing (OR = 2.4; 95% CI = 1.4–3.9; p = 0.001), being a sex worker (OR = 2.3; 95% CI = 1.0–5.4; p = 0.046), and surgery (OR = 1.7; 95% CI = 1.0–2.7; p = 0.042). The HCV subtype distribution was 68.2% for 1a, 15.2% for 3a, 10.6% for 1b, 3.0% for 2b, 1.5% for 2a, and 1.5% for 4a. The advanced liver fibrosis prevalence was highest in patients with HIV/HCV co-infection (47.7%), especially in those with HCV subtype 1a. CD4+ counts, albumin, direct bilirubin, and indirect bilirubin were associated with liver fibrosis. In conclusion, HCV infection had a significant impact on the liver health of Mexican HIV patients, highlighting the need for targeted preventive strategies in this population. [ABSTRACT FROM AUTHOR]

Berberine, a natural alkaloid found abundantly in various medicinal plants, exhibits antioxidative, anti-inflammatory, and lipid metabolism-regulatory properties. Nonetheless, its protective effects and the molecular mechanisms underlying liver injury in fish have not been fully elucidated. The aims of this study were to investigate the antioxidative, anti-inflammatory, and lipid metabolism-regulating effects of berberine against high-fat diet (HFD)-induced liver damage and to clarify the underlying molecular mechanisms. Tilapia were fed diets containing two doses of berberine (50 and 100 mg/kg diet) alongside high fat for 60 days. The results showed that berberine treatments (50 and/or 100 mg/kg) significantly reduced elevated aminotransferases, triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-c) in the plasma. In the liver, berberine treatments significantly increased the expression of peroxisome proliferator-activated receptor α (pparα) and carnitine palmitoyltransferase 1 (cpt-1) genes, leading to a reduction in lipid accumulation. Meanwhile, berberine treatment suppressed lipid peroxidation formation and enhanced antioxidant capacity. Berberine upregulated the mRNA levels of erythroid 2-related factor 2 (nrf2) and its downstream genes including heme oxygenase 1 (ho-1) and glutathione-S-transferase (gstα). Additionally, berberine attenuated the inflammation by inhibiting the expression of toll-like receptor 2 (tlr2), myeloid differential protein-88 (myd88), relb, and inflammatory cytokines such as interleukin-1β (il-1β), tumor necrosis factor-α (tnf-α), and il-8. In summary, this study suggested that berberine offers protection against HFD-induced liver damage in tilapia via regulating lipid metabolism, antioxidant status, and immune response. This protective effect may be attributed to the modulation of the Nrf2, TLR2/MyD88/NF-κB, and PPARα signaling pathways. [ABSTRACT FROM AUTHOR]

In this study, we investigated the hepatoprotective effects of an ethanol extract of Sophora flavescens Aiton (ESF) on an alcohol-induced liver disease mouse model. Alcoholic liver disease (ALD) was caused by the administration of ethanol to male C57/BL6 mice who were given a Lieber−DeCarli liquid diet, including ethanol. The alcoholic fatty liver disease mice were orally administered ESF (100 and 200 mg/kg bw/day) or silymarin (50 mg/kg bw/day), which served as a positive control every day for 16 days. The findings suggest that ESF enhances hepatoprotective benefits by significantly decreasing serum levels of aspartate transaminase (AST) and alanine transaminase (ALT), markers for liver injury. Furthermore, ESF alleviated the accumulation of triglyceride (TG) and total cholesterol (TC), increased serum levels of superoxide dismutase (SOD) and glutathione (GSH), and improved serum alcohol dehydrogenase (ADH) activity in the alcoholic fatty liver disease mice model. Cells and organisms rely on the Kelch-like ECH-associated protein 1- Nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2) system as a critical defensive mechanism in response to oxidative stress. Therefore, Nrf2 plays an important role in ALD antioxidant responses, and its level is decreased by increased reactive oxidation stress (ROS) in the liver. ESF increased Nrf2, which was decreased in ethanol-damaged livers. Additionally, four polyphenol compounds were identified through a qualitative analysis of the ESF using LC-MS/MS. This study confirmed ESF's antioxidative and hangover-elimination effects and suggested the possibility of using Sophora flavescens Aiton (SF) to treat ALD. [ABSTRACT FROM AUTHOR]

Birds have enough conditions to be used as bioindicators for the presence of environmental contaminants. Notably, chlorpyrifos (CPF) remains extensively employed in Argentina, particularly in fruit plantations and livestock settings This study aimed to assess the potential impacts of CPF on common quail (Coturnix coturnix) embryos through external eggshell application during key embryonic stages (days 1, 4, and 14). Concentrations equivalent to those used in fruit applications, 5× and 10 × (38.4, 192, and 384 µg/egg), were employed. A 48% commercial formulation of CPF (Pirfos - Icona®) was utilized. An increase in embryonic deaths, as well as a statistical association between the degree of liver or kidney lesions and CPF concentrations was observed. The results suggest that CPF can induce embryotoxic effects with a single exposure to quail embryos and compromise the viability of the organisms. The study suggests a potential exposure risk for embryos through contact with the insecticide on the eggshell's exterior. [ABSTRACT FROM AUTHOR]

Background and Objectives: Intrahepatic cholestasis of pregnancy (ICP) stands as one of the most prevalent concerns in maternal–fetal medicine, presenting a significant risk to fetal health and often associated with liver dysfunction. Concurrently, the coronavirus-19 (COVID-19) infection can lead to hepatic cell injury through both direct and indirect pathways. Hypothetically, these two conditions may coincide, influencing each other. This study aimed to comparatively assess the incidence and severity of ICP before and during the COVID-19 pandemic. Methods: A retrospective cohort study was conducted, comparing the incidence and severity of ICP between January 2018 and February 2020 (pre-COVID-19 period) and March 2020 to March 2022 (COVID-19 period) across two hospitals, encompassing 7799 deliveries. The diagnosis of ICP was established using the ICD-10 code and defined as total bile acids (BA) levels ≥ 10 μmol/L. Statistical analysis included descriptive statistics, Chi-square and Mann–Whitney U tests, as well as multiple or logistic regression analysis. Results: A total of 226 cases of ICP were identified. The incidence of mild cholestasis (BA < 40 μmol/L) was lower during the pandemic compared to before (3% before versus 2%, p < 0.05), while the incidence of moderate and severe ICP remained unchanged (0.6% before vs. 0.4%, p = 0.2). Overall, the total incidence of ICP was lower during the pandemic (3.6% before versus 2.4%, p = 0.01). No significant differences were observed in severity (as defined by BA and liver function test levels), rates of caesarean section, or neonatal birth weights. Conclusions: During the COVID-19 pandemic, the total incidence of ICP appeared to be lower. However, this reduction was primarily observed in cases of mild ICP, potentially indicating challenges in detection or reduced access to medical services during this period. The incidence of moderate and severe ICP remained unchanged, suggesting that these forms of the condition were unaffected by the pandemic's circumstances. [ABSTRACT FROM AUTHOR]

Arsenic (As) is a highly toxic metalloid that can be found in insufficiently purified drinking water and exerts adverse effects on the physiology of living organisms that can negatively affect human health after subchronic exposure, causing several diseases, such as liver damage. A high‐fat diet, which is increasing in frequency worldwide, can aggravate hepatic pathology. However, the mechanisms behind liver injury caused by the combinatory effects of As exposure and a high‐fat diet remain unclear. In this study, we investigated such underlying mechanisms by focusing on three different aspects: As biotransformation, pathological liver damage, and differential expression of signaling pathway components. We employed mice that were fed a regular diet or a high‐fat diet and exposed them to a range of arsenite concentrations (As(III), 0.05–50 mg/L) for 12 weeks. Our results showed that a high‐fat diet increased the absorption of As into the liver and enhanced liver toxicity, which became progressively more severe as the As concentration increased. Co‐exposure to a high‐fat diet and As(III) activated PI3K/AKT and PPAR signaling as well as fatty acid metabolism pathways. In addition, the expression of proteins related to lipid cell function, lipid metabolism, and the regulation of body weight was also affected. Our study provides insights into the mechanisms that contribute to liver injury from subchronic combinatory exposure to As and a high‐fat diet and showcases the importance of a healthy lifestyle, which may be of particular benefit to people living in areas with high As(III) concentrations, as a means to reduce or prevent aggravated liver damage. [ABSTRACT FROM AUTHOR]

Hepatitis D virus (HDV) infection represents the most severe form of chronic viral hepatitis. We have shown that the delivery of HDV replication-competent genomes to the hepatocytes using adeno-associated virus (AAV-HDV) as gene delivery vehicles offers a unique platform to investigate the molecular aspects of HDV and associated liver damage. For the purpose of this study, we generated HDV genomes modified by site-directed mutagenesis aimed to (i) prevent some post-translational modifications of HDV antigens (HDAgs) such as large-HDAg (L-HDAg) isoprenylation or short-HDAg (S-HDAg) phosphorylation; (ii) alter the localization of HDAgs within the subcellular compartments; and (iii) inhibit the right conformation of the delta ribozyme. First, the different HDV mutants were tested in vitro using plasmid-transfected Huh-7 cells and then in vivo in C57BL/6 mice using AAV vectors. We found that Ser177 phosphorylation and ribozymal activity are essential for HDV replication and HDAg expression. Mutations of the isoprenylation domain prevented the formation of infectious particles and increased cellular toxicity and liver damage. Furthermore, altering HDAg intracellular localization notably decreased viral replication, though liver damage remained unchanged versus normal HDAg distribution. In addition, a mutation in the nuclear export signal impaired the formation of infectious viral particles. These findings contribute valuable insights into the intricate mechanisms of HDV biology and have implications for therapeutic considerations. [ABSTRACT FROM AUTHOR]

Milkfish (Chanos chanos) is valued in aquaculture for its affordability and nutritional richness. However, conventional farming techniques frequently result in suboptimal yields due to lead (Pb) contamination. Traditional milkfish ponds are typically situated near coastal areas, river waters, estuaries, ports, and industrial zones, rendering them susceptible to contamination, particularly from heavy metals, like Pb. This study aimed to analyze Pb accumulation in the body of milkfish juvenile, identify liver and gills damage, and examine the growth rate and survival of milkfish exposed to Pb at various concentrations. Juvenile milkfish were exposed to various concentrations of PbNO3, namely 0 mL.L-1, 0.08 mL.L-1, 0.8 mL.L-1, and 8 mL.L-1, including the non-exposed control group. The metal content of the fish bodies was measured using an AA spectrophotometer. Histological analysis of the liver and gills of the fish was performed to evaluate organ damage. The results showed significant Pb accumulation has been observed in milkfish exposed to high Pb concentrations. The control treatments showed a decrease in metal content, whereas treatments with high concentrations showed a significant increase. Exposure to Pb within 30 d can cause organ damage, such as inflammatory cells, secondary lamella fusion, and necrosis that occurs in the gills. In the liver, there is damage such as the accumulation of inflammatory cells, necrosis, and hydrofic degeneration. Pb exposure rapidly damages and disrupts milkfish's biological functions, influencing survival and growth. Pb exposure with doses 8 mL.L-1 significantly affected juvenile milkfish within approximately 60 min. [ABSTRACT FROM AUTHOR]

Sucralose is a food additive initially used to mitigate glycemic peaks and calorie intake in patients with diabetes and obesity. Although sucralose has been considered safe for human consumption, the World Health Organization (WHO) issued a global alert in 2023 concerning the potential health implications of this artificial sweetener. This review aims to comprehensively explore the effects of sucralose intake on human health by understanding sucralose absorption, metabolism, and excretion. We also outline the role of the sweet taste 1 receptor 3 (T1R3) in mediating sucralose-dependent signaling pathways that regulate satiety, incretin release, and insulin response. Finally, we discuss the impact of sucralose on microbiome dysbiosis, inflammatory response origin, liver damage, and toxicity. Gaining a deeper understanding of the manifold effects of sucralose on human physiology will help promote further studies to ensure its consumption is deemed safe for a broader population, including children, adolescents, and pregnant women. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the mineral profile and histopathological findings in the liver of Leptodactylus macrosternum (white-lipped frog) and to assess the association between melanomacrophage areas and hepatic fungal granuloma with several factors such as weight, snout-cloacal length, sex, hepatosomatic index, season (dry and rainy), and condition factor K. A total of 135 frogs of different ages were collected from three areas in the city of Petrolina, Pernambuco, with varying land use (conventional agriculture, organic agriculture, and Caatinga stricto sensu). The liver of all specimens exhibited changes such as granulomatous lesions, inflammatory cell infiltrate, blood vessel congestion, and sinusoid dilation. The melanomacrophage areas were influenced by weight, snout-cloacal length, and hepatosomatic index. Our findings revealed a positive correlation between body size (weight and snout-cloacal length) and melanomacrophage/hepatic granuloma, while the hepatosomatic index showed a negative relationship. For the condition factor K, only age presents relationship. Eleven elements were quantified for the mineral profile, with aluminum (Al), iron (Fe), and zinc (Zn) being the most abundant in both liver and muscle. Although the histopathological findings and mineral profile of the liver and muscle in this study indicate an effect on the health of L. macrosternum in different collection areas, confirming the relationship between environmental characteristics and these findings requires future studies. Furthermore, long-term studies would be necessary to allow the monitoring of all stages of development of these populations, from tadpoles to adults, for a better evaluation of these effects in L. macrosternum. [ABSTRACT FROM AUTHOR]

Background: Melissa officinalis (MO) is a well-known medicinal plant species used in the treatment of several diseases; it is widely used as a vegetable, adding flavour to dishes. This study was designed to evaluate the therapeutic effect of MO Extract against hyperthyroidism induced by Eltroxin and γ-radiation. Methods: Hyperthyroidism was induced by injecting rats with Eltroxin (100 µg/kg/ day) for 14 days and exposure to γ-radiation (IR) (5 Gy single dose). The hyperthyroid rats were orally treated with MO extract (75 mg/kg/day) at the beginning of the second week of the Eltroxin injection and continued for another week. The levels of thyroid hormones, liver enzymes and proteins besides the impaired hepatic redox status and antioxidant parameters were measured using commercial kits. The hepatic gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its inhibitor Kelch-like ECH-associated protein-1(Keap-1) in addition to hepatic inflammatory mediators including tumor necrosis factor-α (TNF- α), Monocyte chemoattractant protein-1 (MCP-1) and fibrogenic markers such as transforming growth factor-beta1 (TGF-β1) were determined. Results: MO Extract reversed the effect of Eltroxin + IR on rats and attenuated the thyroid hormones. Moreover, it alleviated hyperthyroidism-induced hepatic damage by inhibiting the hepatic enzymes' activities as well as enhancing the production of proteins concomitant with improving cellular redox homeostasis by attenuating the deranged redox balance and modulating the Nrf2/Keap-1 pathway. Additionally, MO Extract alleviated the inflammatory response by suppressing the TNF- α and MCP-1 and prevented hepatic fibrosis via Nrf2-mediated inhibition of the TGF-β1/Smad pathway. Conclusion: Accordingly, these results might strengthen the hepatoprotective effect of MO Extract in a rat model of hyperthyroidism by regulating the Nrf-2/ Keap-1 pathway. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the relationship between alanine aminotransferase and related biochemical parameters and potential risk factors in women with premature ovarian insufficiency (POI). This is a retrospective cohort study with 126 POI patients (including subclinical POI, n= 27) and 130 healthy controls who visited our clinic between April 2021 to November 2022. Associations were investigated by multiple linear regression, Person correlation analysis, the Kruskal-Wallis test, Mann-Whitney U test, and the independent t-test. When compared to controls, analysis of POI patients showed that body mass index (BMI), uric acid (UA) and urea, alanine aminotransferase (ALT), aspartate aminotransferase (AST), monocyte/lymphocyte ratio, monocyte count (MONO), neutrophil count (NEUT), follicle-stimulating hormone (FSH), luteinizing hormone, and neutrophil/lymphocyte ratio (NLR) were significantly higher, while estradiol (E2), the lymphocyte count and the AST/ALT ratio were lower (P < 0.05). According to linear correlation, it was clear that BMI, FSH, white blood cell count (WBC), NEUT, MONO, UA, AST, and NLR were positively associated with ALT (r = 0.215, 0.388, 0.195, 0.187, 0.184, 0.605, 0.819, and 0.189, respectively, all P < 0.05) while E2 was negatively associated with ALT (r = −0.278, P < 0.05). In addition, multiple linear regression revealed a significant, independent, and positive correlation between AST, FSH, and ALT (B =1.403 and 0.069, respectively, P < 0.05). Analysis revealed that the levels of ALT were significantly higher in POI patients. In addition, BMI, FSH, UA, AST, MONO, NLR, NEUT, and WBC were positively associated with ALT in POI patients. E2 was negatively associated with ALT. Multiple linear regression revealed an independent and positive correlation between AST, FSH, and ALT. In addition, there was also a risk of liver function damage in women with POI and subclinical POI. If patients were diagnosed with POI, early examination and corresponding intervention will be required to effectively prevent the further development of liver disease. [ABSTRACT FROM AUTHOR]

Background: Obesity is a growing global problem that causes various complications such as diabetes, cognitive dysfunction, cardiovascular diseases, and hepatobiliary disease. Alpha-linolenic acid (ALA) has been reported to exhibit multiple pharmaceutical effects. This study aimed to explore the effects of ALA on obesity-induced adipose tissue accumulation, cognitive impairment, inflammation, and colonic mucosal barrier integrity. Methods: Mice were fed with high-fat diet (HFD) and were treated with ALA (60 or 100 mg/kg). Body weight, adipose tissue, serum glucose and lipid levels, glucose resistance, and insulin resistance were measured. Cognitive ability was analyzed using the behavior tests. PTP1B and IRS/p-AKT/p-GSK3β/p-Tau signaling were examined to evaluate inflammation and synaptogenesis. Colon mucosal barrier integrity was examined by Alcian blue staining and expression of the tight junction proteins. The production of pro-inflammatory cytokines and liver damages were evaluated. 3T3-L1 cells were used for in vitro experiments. Cell viability, migration and invasion were detected. The levels of ROS, iron, and ferrous ions were measured to assess ferroptosis. Metabolomic analysis of adipose tissues was performed. Results: ALA treatment prevented HFD-induced adipose tissue accumulation, improved glucose and lipid homeostasis and metabolism. Administration of ALA repressed the HFD-induced increase in insulin levels and insulin resistance index. Serum and colon levels of pro-inflammatory cytokines were decreased after ALA treatment. ALA elevated mitochondrial content in brown adipose tissues. ALA ameliorated obesity-induced cognitive impairment and hippocampal inflammation, enhanced colon mucosa integrity. ALA treatment ameliorated HFD-induced liver damage and lipid accumulation and inhibited differentiation of preadipocyte 3T3-L1 cells into mature adipocytes and induces ferroptosis. Metabolomic analysis suggested that ALA may target the glycerolipid metabolism pathway to ameliorate obesity. Knockdown of AGPAT2 abolished the protective effects of ALA. Conclusion: ALA treatment suppressed adipose accumulation in adipocytes, improved cognitive ability and colon integrity, and alleviated liver damage by modulating the 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2). [ABSTRACT FROM AUTHOR]

Background: Liver damage is indicated by histopathological and metabolic dysfunction. There has been increasing interest in natural hepatoprotective agents from medicinal herbs. The medicinal plant Cistus ladanifer widely used in phytotherapy was selected for this study. Objectives: The work aims to investigate the hepatoprotective effects of Cistus ladanifer leaf extracts in vivo against the paracetamol-induced hepatotoxicity mice and in silico using the docking method. The chemical composition of the extracts was also studied. Materials and methods: The paracetamol-induced hepatotoxicity mice were treated with aqueous and methanolic extracts of Cistus ladanifer at two doses of 150 and 300 mg/kg body. The serum levels of aspartate aminotransferase, alanine aminotransferase, triglycerides, total cholesterol, urea, and creatinine in mice-induced hepatotoxicity were measured to evaluate the hepatoprotective activity of the extracts. The histopathological alterations were also investigated. The chemical profile of methanolic and aqueous C. ladanifer extracts was determined using GC-MS. The Human Cytochrome P450 2E1(CYP2E1) was presented as a protein target and the docking was studied using Maestro version 11.5 software developed by Schrodinger, LLC. Results: The administration of C. ladanifer extracts showed hepatic protection at an oral dose of 150 and 300 mg/kg for the aqueous extract and only at 150 mg/kg for the methanolic one. The aqueous extract at both doses and the methanolic extract at 150 mg/kg didn't occur any biochemical or histological alterations. However, the methanolic extract showed hepatic toxicity at 300 mg/kg. Various compounds were identified in the methanolic and the aqueous extracts, probably responsible of the hepatoprotective activity. The in silico study has also shown that some molecules present in both extracts presented a good affinity in the active site of Cytochrome P450 2E1 (CYP2E1). Conclusion: The results deserve more attention as C. ladanifer can be considered a source of pharmacological compounds with hepatoprotective effects. Further detailed investigation is needed to deepen the study. [ABSTRACT FROM AUTHOR]

Benzo[a]pyrene (B[a]P), a highly carcinogenic polycyclic aromatic hydrocarbon primarily formed during incomplete organic matter combustion, undergoes a series of hepatic metabolic reactions once absorbed into the body. B[a]P contributes to liver damage, ranging from molecular DNA damage to the onset and progression of various diseases, including cancer. Specifically, B[a]P induces oxidative stress via reactive oxygen species generation within cells. Consequently, more research has focused on exploring the underlying mechanisms of B[a]P-induced oxidative stress and potential strategies to counter its hepatic toxicity. Flavonoids, natural compounds abundant in plants and renowned for their antioxidant properties, possess the ability to neutralize the adverse effects of free radicals effectively. Although extensive research has investigated the antioxidant effects of flavonoids, limited research has delved into their potential in regulating B[a]P metabolism to alleviate oxidative stress. This review aims to consolidate current knowledge on B[a]P-induced liver oxidative stress and examines the role of flavonoids in mitigating its toxicity. [ABSTRACT FROM AUTHOR]

Background and objective: The effect of SARS-CoV-2 infection on the liver during pregnancy and the impact of SARSCOV- 2-related liver injury during pregnancy on obstetric and neonatal outcomes are not yet clear. The aim of this study was to determine the clinical features of pregnant women at risk of liver injury and to investigate the effect of liver dysfunction on obstetric and perinatal outcomes. Methodology: Pregnant women who were followed up and treated at Selcuk University Medical Faculty Hospital and diagnosed with COVID-19 were determined retrospectively. All pregnant women whose PCR test results were positive between March 1, 2020 and July 31, 2022 were included. A total of 96 PCR positive pregnant women were included in the study. The patients were divided into two groups as those with and without liver damage. Both groups were compared in terms of obstetric and neonatal outcomes. Results: While liver damage findings were observed in 34.4% of the 96 pregnant included in the study; No liver damage was observed in 65.6% of the patients. White blood cell, neutrophil, ferritin, D-dimer, troponin, C-reactive protein, systemic immune-inflammation index, interleukin-6, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase levels were higher in patients with liver injury compared to pregnant women without liver injury. Prematurity, premature rupture of membranes, preterm premature rupture of membranes, preeclampsia and fetal death were observed relatively more in the patient group with liver injury, there was no statistical significiant difference between the groups in terms of these complications. Unfortunately, maternal death occurred in four mothers with liver injury and in one patient without liver injury. Birthweight, APGAR scores and obstetric complication rates were similar between two groups. Conclusion: Our study showed that pregnant patients with liver damage had worse inflammatory response than those without liver damage. Women with elevated liver enzymes tend to have severe disease, but obstetric and perinatal outcomes were similar between groups with and without liver damage. [ABSTRACT FROM AUTHOR]

This narrative review critically examines the current research on the health implications of whey protein (WP) supplementation, with a focus on potential risks and adverse effects. WP, commonly consumed for muscle building and weight loss, has been associated with various health concerns. Our comprehensive analysis involved a thorough search of multiple databases, resulting in the inclusion of 21 preclinical and human studies that collectively offer a detailed overview of WP's health impacts. The review reveals significant findings, such as WP's potential link to liver and kidney damage, alterations in gut microbiota, increased acne incidence, impacts on bone mass, and emotional and behavioural changes. These findings underscore the complexity of WP's effects on human health, indicating both beneficial and detrimental outcomes in relation to different posologies in a variety of settings. Our study suggests caution for the protein intake in situations of hepatic and renal compromised functions, as well as in acne susceptibility, while possible beneficial effects can be achieved for the intestinal microbiota, humoral and behavioural level, and finally bone and muscle mass in elderly. We emphasizes the importance of balanced WP consumption and call for more in-depth research to understand its long-term health effects. Health professionals and individuals considering WP supplementation should be aware of these potential risks and approach its use with informed caution. [ABSTRACT FROM AUTHOR]

Introduction: SARS-CoV-2 unsparingly impacts all areas of medicine. Pregnant women are particularly affected by the pandemic and COVID-19 related liver damage seems to be another threat to maternal and fetal health. The aim of this study is to define liver damage profile including bile acids serum levels in COVID-19 pregnant patients and to determine predictors of disease aggravation and poor obstetrics outcomes. Methods: This study has been carried out in the Obstetrics and Gynecology Department, at the National Medical Institute in Warsaw, Poland between 01.02.2021 and 01.11.2022 The study cohort comprises 148 pregnant patients with COVID-19 and 102 pregnant controls who has been tested negative for SARS-CoV-2. Results: COVID-19 pregnant patients presented liver involvement at admission in 41,9%. Hepatotoxic damage accounted for 27 (19.85%), cholestatic type was diagnosed in 11 (8.09%) and mixed type of liver injury was presented in 19 (13.97%) of patients. Higher serum levels of AST, ALT, GGT, total bilirubin and bile acids as well as mixed type of liver injury at admission were correlated with severe form of an illness. AST and ALT above upper reference limit as well as hepatotoxic type of liver damage predisposed pregnant patients with COVID-19 to poor obstetrics outcomes. Conclusion: Hepatic damage in pregnant women with COVID-19 is a common, mild, transaminase-dominant, or mixed type of injury, and often correlates with elevated inflammatory markers. SARS-CoV-2 test should be performed as a part of differential diagnosis in elevated liver function tests. Although bile acids serum levels were commonly elevated they seems to be clinically irrelevant in terms of pregnancy outcomes. DaRpyovs-oA9XgYzu_a_v9 Video Abstract [ABSTRACT FROM AUTHOR]

Background: Orlistat (ORL) is an effective irreversible inhibitor of the lipase enzyme, and it possesses anticancer effects and limited aqueous solubility. This study was designed to improve the aqueous solubility, oral absorption, and tissue distribution of ORL via the formulation of nanocrystals (NCs). Methods: ORL-NC was prepared using the liquid antisolvent precipitation method (bottom-up technology), and it demonstrated significantly improved solubility compared with that of the blank crystals (ORL-BCs) and untreated ORL powder. The biodistribution and relative bioavailability of ORL-NC were investigated via the radiolabeling technique using Technetium-99m (99mTc). Female Swiss albino mice were used to examine the antitumor activity of ORL-NC against solid Ehrlich carcinoma (SEC)-induced hepatic damage in mice. Results: The prepared NCs improved ORL's solubility, bioavailability, and tissue distribution, with evidence of 258.70% relative bioavailability. In the in vivo study, the ORL-NC treatment caused a reduction in all tested liver functions (total and direct bilirubin, AST, ALT, and ALP) and improved modifications in liver sections that were marked using hematoxylin and eosin staining (H&E) and immunohistochemical staining (Ki-67 and ER-α) compared with untreated SEC mice. Conclusions: The developed ORL-NC could be considered a promising formulation approach to enhance the oral absorption tissue distribution of ORL and suppress the liver damage caused by SEC. [ABSTRACT FROM AUTHOR]

We investigated possible protective effects of chlorogenic acid (CGA) against cyclophosphamide (CP) induced hepatic injury in mice. We measured aminotransferase alanine transaminase (ALT) and aspartate transaminase (AST) levels in the serum. We assayed catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in hepatic tissue. We assessed expression of nuclear transcription factor 2 (Nrf2) and Kelch sample related protein-1 (keap1) proteins in hepatic tissues using immunohistochemistry. The relative mRNA expression levels of heme oxygenase-1 (HO-1), NADH quinone oxidoreductase 1 (NQO1), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Hematoxylin & eosin staining was used to assess liver histopathology. We found that administration of CGA prior to induction of injury by CP decreased serum ALT, AST and MDA expressions in hepatic tissue, while CAT, SOD, GSH and GSH-Px concentrations were increased. We found that hepatocytes of animals administered CGA gradually returned to normal morphology. CGA increased the protein expression of Nrf2 in murine hepatic tissue. Administration of CGA up-regulated mRNA expression levels of HO-1, NQO1, TNF-α and IL-6 in hepatic tissue. CGA exhibited a marked protective effect on CP induced liver injury in mice. [ABSTRACT FROM AUTHOR]

Copyright of Revista Nutrición Clínica y Dietética Hospitalaria is the property of Sociedad Espanola de Dietetica y Ciencias de la Alimentacion and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Istanbul Faculty of Medicine / İstanbul Tıp Fakültesi Dergisi is the property of Istanbul Tip Fakultesi Dergisi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: Hepatitis B, caused by the Hepatitis B virus (HBV), can harm the liver without noticeable symptoms. Early detection is crucial to prevent transmission and enhance recovery. The main goal is to predict Hepatitis B through cost-effective lab test data, by utilizing machine learning. The primary focus is on evaluating the effectiveness of various algorithms in predicting the disease and their potential to enhance early diagnosis capabilities. Methods: Six distinct algorithms (Support Vector Machine, K-nearest Neighbors, Logistic Regression, decision tree, extreme gradient boosting, random forest) were employed alongside an ensemble model. Analysis involved two rounds: considering all features and key attributes. The Synthetic Minority Oversampling Technique (SMOTE) was employed for data imbalance. Various metrics, including the confusion matrix, precision, recall, F1 score, accuracy, receiver operating characteristics (ROC) curve, area under the curve (AUC), and mean absolute error (MAE), were utilized to assess the efficacy of each predictive technique. The National Health and Nutrition Examination Survey (NHANES) dataset was employed. Results: The experimental results demonstrate that the ensemble model attained the highest accuracy (97%) and AUC (0.997) in comparison to existing models. The analysis revealed that specific crucial features possess substantial predictive significance within this model. Conclusion: The study underscores the potential of the ensemble model as a valuable tool for medical practitioners, leveraging cost-effective and readily obtainable laboratory test data to predict Hepatitis B with remarkable accuracy. By facilitating early diagnosis and intervention, this research presents a promising avenue to enhance patient outcomes in the context of Hepatitis B. [ABSTRACT FROM AUTHOR]

The coronavirus disease of 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), includes a clinical spectrum of diseases from mild to severe progressive pneumonia, which has affected and still affects the human population worldwide. Most commonly, it is presented by respiratory symptoms, but studies have shown that about 50% of patients with SARS-CoV-2 infection have at least one gastrointestinal symptom (GI), predominantly nausea, diarrhea, vomiting, or loss of appetite. In addition, abnormal liver functional tests are commonly present in the SARS-CoV-2 virus. The aim of our study was to examine the GI and hepatic manifestations of COVID-19 in patients hospitalized due to COVID-19 pneumonia in "COVID hospital Batajnica", University Clinical Center of Serbia in Belgrade. The study included 498 consecutive patients, and the data was obtained from the patient's electronic medical history. GI symptoms included nausea, vomiting, diarrhea, and anorexia. Collected laboratory values included baseline and peak values of blood count, inflammatory parameters, liver function tests, renal function tests, and cardiac enzyme tests. The results have shown that GI symptoms occurred in 26% of cases at diagnosis, which indicates the great susceptibility of the GI system to SARS-CoV-2. There was a high risk of liver injury in patients with COVID-19 pneumonia (>60%). The level of AST is more often increased compared to ALT, which is different from other virus-induced liver lesions and may be a useful indicator of SARS-CoV-2 infection. Further research should focus on the causes of liver damage in SARS-CoV-2 virus and the impact on treatment and outcome of COVID-19 disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Modern broilers are vulnerable to various stressor agents which may disturb their antioxidant system and lead to poor performance. Supplementation with feed additives which can improve broilers' antioxidant response can be an effective nutritional intervention. This study evaluated the performance, fat, and blood parameters of broilers fed diets supplemented with the antioxidant hydroxytyrosol. Hydroxytyrosol supplementation improved meat quality through the reduction of fatty acid content of breast meat and, moreover, improved liver function through the reduction of enzymes related to liver health. Therefore, hydroxytyrosol supplementation can be used as a potent feed additive capable of reducing the oxidative stress caused by the intensive production system. The study aimed to evaluate the effects of dietary supplementation of hydroxytyrosol (HT) on performance, fat, and blood parameters of broilers. In total, 960 male chicks were distributed into four treatments groups with 12 replicates with 20 birds per pen, with varying HT levels (0, 5, 10, and 50 mg/kg of feed) added to the basal diet from 1 to 42 days old. Feed intake, body weight gain, and feed conversion ratio were evaluated. Enzymes related to liver injury were evaluated in blood. Fatty acid profile and malondialdehyde (MDA) concentration were determined in the breast meat. Dietary supplementation of HT did not improve broilers' performance (p > 0.05). Birds fed 50 mg HT/kg had lower AST, ALT, and GGT concentrations (p ≤ 0.05), whereas broilers fed 5, 10, and 50 mg HT/kg, had lower TBIL concentrations (p ≤ 0.05). Breast meat of broilers fed 50 mg HT/kg had lower lipid content, saturated fatty acid, unsaturated fatty acids, MDA concentrations (p ≤ 0.05), and polyunsaturated fatty acids (p < 0.0001). In summary, supplementation of 5, 10, and 50 mg HT/kg does not improve the performance of broilers, but the dose of 50 mg HT/kg helps the liver against inflammation and improves fat parameters. [ABSTRACT FROM AUTHOR]

Introduction: The Hippo pathway and its transcriptional effectors yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are targets for cancer therapy. It is important to determine if the activation of one factor compensates for the inhibition of the other. Moreover, it is unknown if YAP/TAZ-directed perturbation affects cell–cell communication of non-malignant liver cells. Materials and Methods: To investigate liver-specific phenotypes caused by YAP and TAZ inactivation, we generated mice with hepatocyte (HC) and biliary epithelial cell (BEC)-specific deletions for both factors (YAPKO, TAZKO and double knock-out (DKO)). Immunohistochemistry, single-cell sequencing, and proteomics were used to analyze liver tissues and serum. Results: The loss of BECs, liver fibrosis, and necrosis characterized livers from YAPKO and DKO mice. This phenotype was weakened in DKO tissues compared to specimens from YAPKO animals. After depletion of YAP in HCs and BECs, YAP expression was induced in non-parenchymal cells (NPCs) in a cholestasis-independent manner. YAP positivity was detected in subgroups of Kupffer cells (KCs) and endothelial cells (ECs). The secretion of pro-inflammatory chemokines and cytokines such as C-X-C motif chemokine ligand 11 (CXCL11), fms-related receptor tyrosine kinase 3 ligand (FLT3L), and soluble intercellular adhesion molecule-1 (ICAM1) was increased in the serum of YAPKO animals. YAP activation in NPCs could contribute to inflammation via TEA domain transcription factor (TEAD)-dependent transcriptional regulation of secreted factors. Conclusion: YAP inactivation in HCs and BECs causes liver damage, and concomitant TAZ deletion does not enhance but reduces this phenotype. Additionally, we present a new mechanism by which YAP contributes to cell–cell communication originating from NPCs. [ABSTRACT FROM AUTHOR]

In this research, the influence of hirsutidin on mice with alcoholic liver disease was examined. A total of 30 mice were randomly allocated to five groups (n = 6): Normal control group, Ethanol (EtOH) control group, hirsutidin-10, hirsutidin-20, and hirsutidin-20 per se for 4-week. Further-more, 1 h after the last dosage of the treatment, 5 mL/kg (i.p.) EtOH (56%) was injected to cause hepatic injury. After 5 h of EtOH administration, blood samples were taken, and then the liver was excised for biochemical analysis. Hirsutidin treatment restored the biochemical changes induced by EtOH: serum levels of liver function tests, lipid profile, blood urea nitrogen, antioxidants levels, malondialdehyde, and cytokines. Hirsutidin supplementation also significantly decreased the histopathological abnormalities in EtOH-induced mice. In the present study, hirsutidin was found to have therapeutic potential for the treatment of alcoholic liver disease. Hirsutidin prevented ethanol-induced biochemical and histopathological alterations in the liver, suggesting its hepatoprotective effect. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to investigate the relationship between preoperative aspartate aminotransferase-to-platelet ratio index (APRI) and postoperative complications following total hip arthroplasty (THA). Methods: All THA for osteoarthritis patients from 2007 to 2020 within the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database were included in this study. Subjects were subsequently divided into cohorts based on APRI. Four groups, including normal range, some liver damage, significant fibrosis, and cirrhosis groups, were created. Comparisons between groups were made for demographics, past medical history, and rate of major and minor complications. Other outcomes included readmission, reoperation, discharge destination, mortality, periprosthetic fracture, and postoperative hip dislocation. Multivariate logistic regression analysis was performed to determine the role of preoperative APRI in predicting adverse outcomes. Statistical significance was set at p < 0.05. Results: In total, 104,633 primary THA patients were included in this study. Of these, 103,678 (99.1%) were in the normal APRI group, 444 (0.4%) had some liver damage, 256 (0.2%) had significant fibrosis, and 253 (0.2%) had cirrhosis. When controlling for demographics and relevant past medical history, the abnormal APRI groups had a significantly higher likelihood of major complication, minor complication, intraoperative or postoperative bleeding requiring transfusion, readmission, and non-home discharge (all p < 0.05) compared to normal APRI individuals. Conclusions: Abnormal preoperative APRI is linked with an increasing number of adverse outcomes following THA for osteoarthritis for patients across the United States. Level of evidence: Level I [ABSTRACT FROM AUTHOR]

Introduction: Fluoride is known to affect the nervous system, kidneys, liver, and gastrointestinal system, in addition to teeth and bones, when consumed in amounts exceeding 1 ppm per day over a prolonged period. YSR Kadapa district has been identified as one of the districts with endemic fluoride areas in Andhra Pradesh, India, by the Central Groundwater Board of India. Aim: To assess the toxic effects of fluoride on liver function in individuals affected and unaffected by dental fluorosis, who consume high levels of fluoride in water, in the endemic fluoride rural areas of YSR Kadapa district. Materials and Methods: A cross-sectional study was conducted in six villages of YSR Kadapa district, where the drinking water has elevated fluoride content. A total of 320 subjects were selected as study participants. The subjects were divided into two groups based on age and dental fluorosis: Group A, aged between 21 and 40 years, and Group B, aged between 41 and 60 years. Subjects of each group were further sub-grouped according to presence or absence of fluorosis. The selected subjects were screened for dental fluorosis, and Groups A and B were further divided into subgroups based on the presence or absence of dental fluorosis. Blood samples were collected from the participants to assess liver function using serum levels of liver function markers such as total bilirubin (direct and indirect), Serum Glutamic Oxaloacetic Transaminase (SGOT), Serum Glutamate Pyruvate Transaminase (SGPT), and Alkaline Phosphatase (ALP). Water and urine samples were also tested for fluoride levels using a fluoride ion meter. Statistical significance was determined using the t-test. Results: The mean fluoride levels in the water samples from the study areas ranged from 1.55±0.30 mg/L to 4.10±0.20 mg/L, and the urinary fluoride levels in the urine samples ranged from 0.54±0.46 mg/L to 2.13±0.845 mg/L. Among the study subjects, 60.6% (194) were affected by dental fluorosis, with 58.66% (88) belonging to Group A and 62.35% (106) belonging to Group B. There was no statistically significant difference in liver function markers in the serum between subjects with dental fluorosis and those without dental fluorosis in both groups (p>0.05), and the levels were within the normal reference range. Conclusion: This study found no impaired or altered liver function in adults affected by dental fluorosis and adults unaffected by dental fluorosis who consumed water with high levels of fluoride in the YSR Kadapa district. [ABSTRACT FROM AUTHOR]