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Resveratrol effectively attenuates α-naphthyl- isothiocyanate-induced acute cholestasis and liver injury through choleretic and anti-inflammatory mechanisms
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Resveratrol effectively attenuates α-naphthyl- isothiocyanate-induced acute cholestasis and liver injury through choleretic and anti-inflammatory mechanisms
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Resveratrol effectively attenuates α-naphthyl- isothiocyanate-induced acute cholestasis and liver injury through choleretic and anti-inflammatory mechanisms
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Journal Article
Resveratrol effectively attenuates α-naphthyl- isothiocyanate-induced acute cholestasis and liver injury through choleretic and anti-inflammatory mechanisms
2014
Overview
Aim： α-Naphthylisothiocyanate （ANIT） is a well-characterized cholestatic agent for rats. The aim of this study was to examine whether resveratrol could attenuate ANIT-induced acute cholestasis and liver injury in rats. Methods： SD rats were treated with resveratrol （15 or 30 mg/kg, ip） or a positive control drug ursodeoxycholic acid （100 mg/kg, po） for 5 consecutive days followed by a single dose of ANIT （60 mg/kg, po）. Bile flow, and serum biochemical markers and bile constituents were measured 48 h after ANIT administration. Hepatic levels of oxidative repair enzymes （glutathione peroxidase, catalase and MnSOD）, myeloperoxidase activity, TNF-α, IL-6, and ATP content, as well as the expression of liver transporter genes and proteins were assayed. Results： ANIT exposure resulted in serious cholestasis and liver injury, as shown by marked neutrophil infiltration in liver, dramatically increased serum levels of ALT, AST, GGT, ALP, TBA, TBIL, IBIL, and DBIL, and significantly decreased bile excretion and biliary output of GSH and HCO3-. ANIT significantly increased TNF-α and IL-6 release and myeloperoxidase activity, decreased mitochondrial biogenesis in liver, but had little effect on hepatic oxidative repair enzymes and ATP content. Furthermore, ANIT significantly decreased the expression of Mrp2, FXR, and CypTal, markedly increased Mrp3 expression in liver. Pretreatment with resveratrol attenuated ANIT- induced acute cholestasis and liver injury, and other pathological changes. Pretreatment with ursodeoxycholic acid was less effective. Conclusion： Resveratrol effectively attenuates ANIT-induced acute cholestasis and liver injury in rats, possibly through suppression of neutrophil infiltration, as well as upregulation of expression of hepatic transporters and enzymes, thus decreasing accumulation of bile acids.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Adenosine Triphosphate - metabolism
/ Animals
/ Anti-Inflammatory Agents - pharmacology
/ Biomedical and Life Sciences
/ Chemical and Drug Induced Liver Injury - blood
/ Chemical and Drug Induced Liver Injury - etiology
/ Chemical and Drug Induced Liver Injury - genetics
/ Chemical and Drug Induced Liver Injury - pathology
/ Chemical and Drug Induced Liver Injury - prevention & control
/ Cholagogues and Choleretics - pharmacology
/ Cholestasis - chemically induced
/ Cholestasis - prevention & control
/ DNA, Mitochondrial - metabolism
/ Inflammation Mediators - blood
/ Male
/ Membrane Transport Proteins - drug effects
/ Membrane Transport Proteins - genetics
/ Membrane Transport Proteins - metabolism
/ Neutrophil Infiltration - drug effects
/ Original
/ Oxidative Stress - drug effects
/ Vaccine
/ 异硫氰酸酯
/ 急性
/ 淤积
/ 白藜芦醇
/ 肝损伤
/ 胆汁酸
/ 衰减
