Brain Oxidative Stress Induced by Obstructive Jaundice in Rats

Abstract

The effect of experimental obstructive jaundice on the oxidative status of brain tissues in rats was examined. Twenty-four male Wistar rats were divided into 4 groups: Group I was the control, group II was the sham operated, and groups III and IV were bile duct ligated and killed on the 5th and the 10th day, respectively. Oxidative stress was assessed by measuring the thiol redox state (protein and nonprotein components) and lipid peroxidation level variations in samples from the cerebral cortex, midbrain, and cerebellar tissue in all animals. Results indicated the presence of oxidative stress in the jaundiced animals that was more pronounced on the 10th day as indicated by a decrease in reduced glutathione and protein thiol and an increase in protein disulphide and lipid peroxidation. A dramatic elevation of the level of total nonprotein mixed disulphide level was found specifically in the midbrain in the 10th day group. This suggests an accumulation of nonprotein disulfides other than oxidized glutathione, which remained unchanged, in this particular brain area. This study showed a correlation between experimental obstructive jaundice and the oxidative stress in the rats' brain, implying that a similar pathogenetic mechanism may play a key role in cholestatic liver disease, resulting in hepatic encephalopathy in humans.

Melatonin Ameliorates Bile Duct Ligation-Induced Systemic Oxidative Stress and Spatial Memory Deficits in Developing Rats

“…M1000 group showed lowest plasma GSH levels whereas highest liver GSH levels and GSH/GSSG ratios suggesting melatonin may regulate the hepatic efflux of GSH to prevent liver damage. In contrast to adult BDL-induced cholestatic rat, we could not find a significant difference of MDA levels or GSH/GSSG ratios in either brain cortex or hippocampus (4,6,27). Nevertheless, data from young BDL rats are scarce.…”

“…The increased ROS may cause target organs damage (e.g., brain, heart, and kidney) via systemic circulation (4,6). GSH is a key intracellular antioxidant that is capable of interacting with free radicals to repair membrane lipid peroxides.…”

“…Cholestasis is now recognized as a disorder characterized by liver oxidants overload (1)(2)(3). Furthermore, the oxidative stress in cholestatic liver disease is a systemic phenomenon (4,5), probably encompassing all tissues and organs, even those separated by the blood-brain barrier (6). Similarly, oxidative stress plays an important role in the pathogenesis of toxic liver injury and other hepatic disorders (7).…”

Melatonin prevents brain oxidative stress induced by obstructive jaundice in rats

“…A rise in lipoperoxidation products is observed in extrahepatic tissues, including the kidney and brain, in animals subjected to OJ (Ljubuncic et al, 2000;Montilla et al, 2001). It has been proposed that antioxidant therapy may be useful for preventing the deleterious effect of oxidative stress on the nervous system during OJ (Chroni et al, 2006). Several studies have demonstrated that the administration of melatonin prevents hepatic oxidative stress in OJ Ohta et al, 2003).…”

“…In this sense, recent studies have shown that obstructive jaundice (OJ) exacerbates oxidative stress in the brain, and it has been suggested that free radicals may be involved in the pathogenesis of hepatic encephalopathy (Chroni et al, 2006;Noremberg et al, 2004). The pathogenesis of OJ involves a systemic alteration that affects different extrahepatic tissues.…”