Melatonin modulates the expression of Bcl-2 family proteins in liver after thermal injury in rats

Abstract

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 both in vivo and in vitro . The aim of this study was to investigate the protective effects of melatonin against burn-induced injury in rat liver and whether these changes were associated with oxidative stress and changes in the expression of apoptosis related genes Bcl-2 and Bax. Melatonin (10 mg/kg, i.p.) was applied immediately after 30% of total body surface area (TBSA) burns of male Wistar rats. Malondialdehyde (MDA) as marker of oxidative stress and tumor necrosis factor (TNF- α ) as inflammatory marker were assayed by biochemical methods. The hepatic apoptosis related genes Bcl-2 and Bax using light immunоchistochemistry were investigated, too. Hepatic TNF- α and MDA levels were increased significantly following severe burn. Thermal trauma increased the Bax expression without any changes of anti-apoptotic Bcl-2 protein in sinusoidal endothelial cells (SECs) of burn-treated animals compared with the control group animals as well as elevated ratio Bax/Bcl-2 suggesting the susceptibility of these cells to apoptosis. Melatonin significantly decreased the MDA and TNF- α levels in the liver tissue. It decreased also expression of Bax, increased expression of Bcl-2 and reduced Bax/Bcl-2 ratio. In conclusion, experimental data show that melatonin modulates the expression of Bcl-2 family proteins by increasing anti-apoptotic Bcl-2, inhibits apoptosis and restricts the burn-induced damage.