Cytoprotective effects of melatonin against necrosis and apoptosis induced by ischemia/reperfusion injury in rat liver.
Melatonin protects against organ ischemia; this effect has mainly been attributed to the antioxidant properties of the indoleamine. This study examined the cytoprotective properties of melatonin against injury to the liver caused by ischemia/reperfusion (I/R). Rats were subjected to 60 min of ischemia followed by 5 hr of reperfusion. Melatonin (10 mg/kg) or the vehicle was administered intraperitoneally 15 min before ischemia and immediately before reperfusion. The serum aminotransferase activity and lipid peroxidation levels were increased markedly by hepatic I/R, which were suppressed significantly by melatonin. In contrast, the glutathione content, which is an index of the cellular redox state, and mitochondrial glutamate dehydrogenase activity, which is a maker of the mitochondrial membrane integrity, were lower in the I/R rats. These decreases were attenuated by melatonin. The rate of mitochondrial swelling, which reflects the extent of the mitochondrial permeability transition, was higher after 5 hr of reperfusion but was attenuated by melatonin. Melatonin limited the release of cytochrome c into the cytosol and the activation of caspase-3 observed in the I/R rats. The melatonin-treated rats showed markedly fewer apoptotic (TUNEL positive) cells and DNA fragmentation than did the I/R rats. These results suggest that melatonin ameliorates I/R-induced hepatocytes damage by inhibiting the level of oxidative stress and the apoptotic pathway. Consequently, melatonin may provide a new pharmacological intervention strategy for hepatic I/R injuries.
Kim
Sung-Hwa
SH
College of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, Korea.
Lee
Sun-Mee
SM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology*; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D009336:Necrosis; D010084:Oxidation-Reduction; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*
D008550:Melatonin