Inhibition of Endotoxin-Induced Hepatotoxicity by Melatonin in Rats

Bacterial endotoxin or lipopolysaccharide causes extensive damage to various organs including the liver. This is due to an increased production of tumor necrosis factor α induced- reactive intermediates. These intermediates are known to cause extensive damage to a variety of cellular biomolecules leading to oxidative stress. In the present study, the role of the pineal hormone melatonin was evaluated as an antioxidant against endotoxin induced- hepatotoxicity using Wistar rats. Bacterial endotoxin was injected (i.v) and animals were sacrificed 8h post-challenge. Endotoxemia was associated with a statistically significant rise in the serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and also caused histopathological changes. Administration of melatonin could significantly attenuate these enzymatic and associated histological alterations. Melatonin was administered (i.p) pre and/or post endotoxin challenge. A significant reduction in the levels of malondialdehyde and tumor necrosis factor-α in the hepatic tissue was also observed with melatonin supplementation. Reduction in the levels of endogenous antioxidants such as superoxide dismutase, catalase and reduced glutathione after endotoxin challenge was effectively attenuated by the administration of melatonin. Endotoxin challenge caused a marked increases in the levels of nitrite, and this was significantly lowered by melatonin administration. The above mentioned changes might have resulted in endotoxin associated hepatocellular necrosis which was minimized by melatonin supplementation in the present study.