title: The effect of the red wine polyphenol resveratrol on a rat model of biliary obstructed cholestasis: involvement of anti-apoptotic signalling, mitochondrial biogenesis and the induction of autophagy.
abstract: Mitochondria are known to be involved in cholestatic liver injury. The potential protective effect of resveratrol in cholestatic liver injury and the possible roles of autophagy and apoptosis induction in this process are not yet clear. The aim of this study is to determine whether resveratrol administration after bile duct ligation can reduce cholestasis-induced liver injury through modulating apoptosis, mitochondrial biogenesis and autophagy. A rat model of cholestasis was established by bile duct ligation (BDL) and compared with a sham group receiving laparotomy without BDL, with resveratrol or control treatments following BDL. The expression of proteins involved in the apoptotic and autophagic pathways were analyzed by western blotting. Apoptosis was examined by TUNEL staining. In the resveratrol/BDL group LC3-II upregulation persisted for 1-7 days, Bax was downregulated and catalase was upregulated at 3-7 days after resveratrol treatment. The decline in mitochondrial DNA copy number was reversed at 3-7 days. Caspase 3 expression was significantly downregulated at 3-7 days in the resveratrol group. TUNEL staining showed significant numbers of apoptotic liver cells appeared in livers 3-7 days after BDL and that was decreased by resveratrol treatment. Our results indicate that early resveratrol treatment reverses impaired liver function within hours of BDL.
authors.affiliation: Department of Neurology, College of Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, Kaohsiung, Taiwan.
authors.forename: Tsu-Kung
authors.initials: TK
authors.lastname: Lin
authors.forename: Li-Tung
authors.initials: LT
authors.lastname: Huang
authors.forename: Ying-Hsien
authors.initials: YH
authors.lastname: Huang
authors.forename: Mao-Meng
authors.initials: MM
authors.lastname: Tiao
authors.forename: Kuo-Shu
authors.initials: KS
authors.lastname: Tang
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Liou
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D001343:Autophagy / Q000187:drug effects*; D001663:Bilirubin / Q000097:blood; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D001651:Cholestasis, Extrahepatic / Q000097:blood / Q000188:drug therapy*; D056915:DNA Copy Number Variations / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D000975:Antioxidants; D001219:Aspartate Aminotransferases; D001663:Bilirubin; D053148:Caspase 3; D002374:Catalase; D004272:DNA, Mitochondrial; D008869:Microtubule-Associated Proteins; D000077185:Resveratrol; D013267:Stilbenes; D051028:bcl-2-Associated X Protein; C494828:Bax protein, rat; C526109:Anxa3 protein, rat; C505410:Casp3 protein, rat