Pharmacological postconditioning with diazoxide attenuates ischemia/reperfusion‑induced injury in rat liver

Tian,Y. S.; Rong,T. Z.; Hong,Y. L.; Min,L.; Jian,P. G.

doi:10.3892/etm.2013.941

Pharmacological postconditioning with diazoxide attenuates ischemia/reperfusion‑induced injury in rat liver

Authors:
- Y. S. Tian
- T. Z. Rong
- Y. L. Hong
- L. Min
- P. G. Jian
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Affiliations: Chongqing Key Laboratory of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, P.R. China, Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, P.R. China
Published online on: January 31, 2013 https://doi.org/10.3892/etm.2013.941
Pages: 1169-1173

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Abstract

It has been demonstrated that ischemic postconditioning (IPO) is capable of attenuating ischemia/reperfusion (I/R) injury in the heart. However, the novel role of pharmacological postconditioning in the liver remains unclear. In this study, the hypothesis that diazoxide postconditioning reduces I/R‑induced injury in rat liver was tested. Rats were assigned randomly to the sham‑operated control, I/R (occlusion of the porta hepatis for 60 min, followed by a persistent reperfusion for 120 min), diazoxide ischemic postconditioning (DIPO; occlusion of the porta hepatis for 60 min, then treatment with diazoxide for 10 min reperfusion, followed by a persistent reperfusion for 110 min) or 5‑hydroxydecanoate (5‑HD)+DIPO (occlusion of the porta hepatis for 60 min, then treatment with diazoxide and 5‑HD for 10 min reperfusion, followed by a persistent reperfusion for 110 min) groups. The alanine aminotransferase (ALT) and aspartate transaminase (AST) levels were assayed. The expression levels of protein kinase c‑ε (pkc‑ε), cytochrome c (cyt‑c), caspase‑3 and bcl‑2 protein were determined by western blotting. The serum levels of ALT and AST and expression levels of cyt‑c and caspase‑3 were significantly lower in the DIPO group (P<0.05). However, the protein expression levels of pkc‑ε and bcl‑2 were markedly increased in the DIPO group (P<0.05). 5‑HD abrogated the protective effects of DIPO. The data of the present study provide the first evidence that DIPO protects the liver from I/R injury by opening the mitochondrial KATP channels, activating and upregulating pkc‑ε and inhibiting the activation of the apoptotic pathway by decreasing the release of cyt‑c and the expression of caspase‑3 and increasing bcl‑2 expression.

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