title: Pharmacological postconditioning with diazoxide attenuates ischemia/reperfusion-induced injury in rat liver.
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 KATPchannels, 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.
authors.affiliation: Chongqing Key Laboratory of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Y S
authors.initials: YS
authors.lastname: Tian
authors.forename: T Z
authors.initials: TZ
authors.lastname: Rong
authors.forename: Y L
authors.initials: YL
authors.lastname: Hong
authors.forename: L
authors.initials: L
authors.lastname: Min
authors.forename: P G
authors.initials: PG
authors.lastname: Jian
keywords: diazoxide; ischemic postconditioning; liver; reperfusion injury