Melatonin Protects Against Taurolithocholic-Induced Oxidative Stress in Rat Liver

Cholestasis. encountered in a variety of clinical disorders, is characterized by intracellular accumulation of toxic bile acids in the liver. Furthermore, oxidative stress plays an important role in the pathogenesis of bile acids Taurolithocholic acid (TLC) was revealed in previous studies as the most pro-oxidative bile acid. Melatonin, a well-known antioxidant, is a safe and widely used therapeutic agent Herein, we investigated the hepatoprotective role of melatonin on lipid and protein oxidation induced by TLC alone and in combination with FeCl3 and ascorbic acid in rat liver homogenates and hepatic membranes. The lipid peroxidation products, malondialdehyde and 4-hydroxyalkenals (MDA + 4-HDA). and carbonyl levels were quantified as indices of oxidative damage to hepatic lipids and proteins, respectively In the current study, the rise in MDA 4-HDA levels induced by TLC was inlubited by melatonin in a concentration-dependent manner in both liver homogenates and in hepatic membranes. Melatonin also had protective effects against structural damage to proteins induced by TLC in membranes These results suggest that the indoleamine melatotnin may potentially act as a protective agent in the therapy of those diseases that involve bile acid toxicity. J. Cell. Biochem. 110: 1219-1225, 2010. (C) 2010 Wiley-Liss, Inc.