Cytoprotective effects of melatonin against necrosis and apoptosis induced by ischemia/reperfusion injury in rat liver

Abstract

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.

Melatonin with 1,25-Dihydroxyvitamin D3 Protects against Apoptotic Ischemia–Reperfusion Injury in the Rat Kidney

“…26 In various experimental studies, Mel has been shown to decrease apoptosis via inhibiting caspase-3 activity. 6,28 In our study, the demonstration that pretreatment of rats with Mel prevents caspase-3-dependent cell apoptosis suggests that the mechanisms of Mel's action may involve a caspasesignaling cascade. Similar results were reported by Kunduzova et al 6 We may suggest that the antioxidant effect of Mel might be in part of its antiapoptotic action.…”

Effective melatonin protection of burn-induced hepatic disorders in rats

“…The cytoprotective effect of melatonin on ischemia/ reperfusion-induced hepatic injury is related to its ability to decrease proinflammatory cytokine production and lipid peroxidation and to inhibit apoptosis [21]. In addition, melatonin protects against alcoholic hepatic injury by attenuating oxidative damage, inflammatory response and apoptosis [22].…”

Melatonin Inhibits mTOR-Dependent Autophagy during Liver Ischemia/Reperfusion

“…We previously showed that MLT inhibits necrotic and apoptotic cell death in a rat model of liver I/R by alleviating levels of oxidative stress [15]. Recently, a protective role of MLT has been reported in cold liver I/R through suppression of endoplasmic reticulum (ER) stress and enhanced autophagy [16].…”