Resveratrol ameliorates hepatic injury via the mitochondrial pathway in rats with severe acute pancreatitis.
To gain insight into the processes by which severe acute pancreatitis induced apoptosis takes place in the liver, and to observe the protective effect of resveratrol on hepatic injury, a rat model of severe acute pancreatitis was induced by administering 4% sodium taurocholate through the common biliopancreatic duct. Pancreatic and hepatic injury was assessed by histology. Serum ALT (alanine aminotransferase), AST (aspartate aminotransferase) and total bilirubin were determined by reaction rate assay, and the serum levels of TNF-alpha (tumor necrosis factor-alpha) and IL-6 (interleukin-6) were detected by ELISA (enzyme linked immunosorbent assay). We investigated cytochrome c released from mitochondria and used the RT-PCR (reverse transcription PCR), Western blot technique to evaluate Bax, Bcl-2, and caspase-3 expression levels in hepatic tissue over the time course of apoptosis. Changes in hepatic cell mitochondrial membrane potential were observed by confocal laser scanning microscopy. The majority of cytochrome c release occurred early in apoptosis from mitochondria, which undergo gradual hepatic impairment. The released cytochrome c can be reduced by resveratrol through both up-regulation of Bcl-2 and down-regulation of Bax and caspase-3. These data provide substantial evidence that apoptosis is involved in hepatic injury during the severe acute pancreatitis process and that resveratrol can ameliorate the situation, thus protecting liver function in rats with severe acute pancreatitis.
Sha
Huanchen
H
Department of Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
Ma
Qingyong
Q
Jha
Rajiv Kumar
RK
Xu
Fuguo
F
Wang
Liancai
L
Wang
Zheng
Z
Zhao
Yan
Y
Fan
Fenling
F
D000208:Acute Disease; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D045304:Cytochromes c / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D010195:Pancreatitis / Q000188:drug therapy* / Q000503:physiopathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D012720:Severity of Illness Index; D013267:Stilbenes / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D019253:Proto-Oncogene Proteins c-bcl-2; D013267:Stilbenes; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D053148:Caspase 3; D000077185:Resveratrol