{'fraction_non_alphanumeric': 0.0358767054067711, 'fraction_numerical': 0.01667508842849924, 'mean_word_length': 5.622073578595318, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Melatonin prevents hepatic injury‐induced decrease in Akt downstream targets phosphorylations

Abstract:  Melatonin 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.