Melatonin protects against taurolithocholic‐induced oxidative stress in rat liver

Abstract

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 FeCl(3) 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 inhibited 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 melatonin may potentially act as a protective agent in the therapy of those diseases that involve bile acid toxicity.

Correlation of inflammation parameters and biochemical markers of cholestasis with the intensity of lipid peroxidation in patients with choledocholithiasis

“…Cholestasis syndrome includes liver function disorder due to the obstruction of bile drainage into the intestine, with the consequent retention of bile constituents in liver and their regurgitation in the blood 15,16 .…”

Melatonin restores muscle regeneration and enhances muscle function after crush injury in rats

“…In addition, the absence of fetal malformations during development [29] as well as the low toxicity of melatonin [30] in mature animals makes it a safe molecule for systemic application. Melatonin has good pharmacokinetic properties and can be considered as a nontoxic therapeutic agent [31].…”

The hydroalcoholic extract of watercress attenuates protein oxidation, oxidative stress, and liver damage after bile duct ligation in rats

“…Cholestasis, a functional or mechanical blockage of bile flow in intrahepatic or extrahepatic bile ducts is a disorder of bile secretion and cholepoiesis. 1,2 Intrahepatic accumulation of stagnant bile acids and toxic materials disturbs hepatocyte membrane, discharges reactive oxygen species (ROS) and induces oxidative stress. 3 In spite of differing pathogenic events of cholestasis in chronic liver diseases, hepatocellular injury is an invariable characteristic of cholestasis, initiating liver dysfunction, enhancing fibrogenesis, and eventually leading to liver failure.…”