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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

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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.

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Abbreviations

LC3:

Microtubule associated protein light chain 3

ALP:

Alkaline phosphatase

BDL:

Bile duct ligation

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Acknowledgments

The authors thank Dr M.P. Murphy (MRC Dunn Human Nutrition Unit, Cambridge, UK) for the comments and grammar corrections. This work was supported by grants (CMRPG8A0111, CLRPG870462, CMRPG870883) from the Chang Gung Memorial Hospital, Taiwan. T.K.L. and M.M.T. designed the study, discussed the data, and wrote the manuscript. L.T.H. discussed the data and corrected the manuscript. Y.H.H. and K.S.T. assisted with the samples and performed the study. C.W.L. provided significant advice and statistical analysis.

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None of the authors have conflicts of interest to declare.

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Authors and Affiliations

  1. Department of Neurology, College of Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, Kaohsiung, Taiwan

    Tsu-Kung Lin & Chia-Wei Liou

  2. Department of Pediatrics, College of Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, Kaohsiung, Taiwan

    Li-Tung Huang, Ying-Hsien Huang, Mao-Meng Tiao & Kuo-Shu Tang

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  1. Tsu-Kung Lin
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Correspondence to Mao-Meng Tiao.

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Lin, TK., Huang, LT., Huang, YH. et al. 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. Apoptosis 17, 871–879 (2012). https://doi.org/10.1007/s10495-012-0732-3

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