• Phil-Ok Koh.
• Department of Anatomy, College of Veterinary Medicine, Gyeongsang National University, Jinju, South Korea. pokoh@gnu.ac.kr
• J. Pineal Res. 2011 Sep 1;51(2):214-9.

AbstractMelatonin is a potent scavenger of reactive oxygen species and a strong antioxidant. Melatonin exerts protective effects against damage by the enhancing the Akt signal pathway, thus regulating apoptotic cell death. Akt phosphorylates pro-apoptotic proteins such as Bad and FoxO1 and inhibits the pro-apoptotic functions of these proteins. This study investigated the protective effects of melatonin through Akt and its downstream targets, Bad and FoxO1, in hepatic ischemia-reperfusion (I/R) damage. Adult mice were subjected to 1 h of hepatic ischemia and 3 h of reperfusion. Hepatic ischemia was induced by occlusions of the hepatic artery, portal vein, and bile duct. Melatonin (10 mg/kg, i.p.) or vehicle was administrated 15 min prior to ischemia and just before reperfusion. Serum aspartate aminotransferase and alanine aminotransferase levels were higher in I/R group than in sham-operated group. Melatonin attenuated increases in these levels. Moreover, melatonin attenuates injury-induced increases in positive TUNEL staining in hepatic tissues. Hepatic I/R injury induced reductions in the Akt up-stream target, PDK1 phosphorylation. The levels of phospho-Akt, phospho-Bad, and phospho-FoxO1 were decreased in vehicle-treated animals. However, melatonin prevented hepatic I/R injury-induced decreases in these proteins levels. Moreover, the interaction levels between phospho-Bad and 14-3-3 and between phospho-FoxO1 and 14-3-3 are reduced in vehicle-treated animals, and melatonin attenuated decreases in the binding levels of these proteins. 14-3-3 exerts an anti-apoptotic function by sequestration of Bad and FoxO1. These findings suggest that melatonin exerts protective effects in case of hepatic I/R damage by maintaining the binding of phospho-Bad and 14-3-3 and the binding of phospho-FoxO1 and 14-3-3, thus preventing activation of apoptotic cell death.© 2011 John Wiley & Sons A/S.

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