Mechanisms of Protection With Melatonin By Hepatic Heme-Oxygenase-1 Activation In Burn

Abstract

Background: Melatonin, the principal secretory product of the pineal gland, functions as a potent antioxidant and free radical scavenger. Additionally, the antiapoptotic effect of melatonin has been observed. Several studies show that heme-oxygenase-1 (HO-1) possesses antiapoptotic action and prevents hepatic damages. Recent studies indicate that heme-oxygenase-1(HO-1) inhibits apoptosis and exert hepatoprotective effect. The aim: of this experimental study was to investigate the protective effects of melatonin against burn-induced apoptotic injury and the association between the oxidative stress and the changed expression of hepatic HO-1 in burn rat model. Material and method: Melatonin was applied immediately after the burn. The expression of hepatic 4-hydroxynonenal (4-HNE), as marker of liver peroxidative injury, hepatic HO-1, marker of antioxidant defense and apoptosis-related genes Bcl-2 and Bax was evaluated using light immunоhistochemistry. Results: Burns caused an increased expression of HO-1, 4-HNE, Bax and Bax/Bcl-2 ratio and induced apoptosis of sinusoidal endothelial cells (SECs) in liver tissue. Melatonin treatment augmented the increase in HO-1 expression, decreased both burn-induced peroxidative damage and hepatic apoptosis as evidenced by reduced expression of Bax, enhanced expression of Bcl-2. Conclusion: Our present data suggest that melatonin suppresses burn-induced liver injury through HO-1 activation, attenuation of lipid peroxidation and modification of Bax/Bcl-2 ratio.