Melatonin inhibits endothelin-1 and induces endothelial nitric oxide synthase genes expression throughout hepatic ischemia/reperfusion in rats
The production of reactive oxygen species (ROS) and dysfunction of vasculature play a central role in the pathophysiology of hepatic ischemia/reperfusion (I/R) injury. The aim of this study was to evaluate the beneficial effects of melatonin on reducing liver I/R injury in rats. Four study groups were formed: (1) saline - administered, control group (Control), (2) melatonin-administered group (MEL), (3) saline -administered I/R group (I/R) and (4) melatonin-administered I/R group (MEL+ I/R). Melatonin was injected intraperitoneally (15 mg/kg) 20 min before ischemia and immediately after reperfusion. After reperfusion, blood and ischemic liver tissues were collected. The group subjected to ischemia showed a significant increase in the serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, as well as an increase in hepatic malondialdehyde (MDA) concentration. These increases were significantly inhibited by melatonin. Although, I/R augmented the endothelin-1 (ET-1) gene expression and the level of big endothelin-1 (big ET-1) in liver tissue, melatonin attenuated these increases. Conversely, non-significant decrease in endothelial nitric oxide synthase (eNOS) mRNA expression in I/R group was significantly elevated by melatonin in MEL+ I/R group. Melatonin exerts beneficial effects on ischemia/reperfusion liver injury through its anti-oxidative function as well as regulation of hepatic microcirculation.
Key words: Melatonin, oxidative stress, ischemia/reperfusion injury, endothelin and nitric oxide synthase.