title: Preventive effect of N-acetyl-L-cysteine on oxidative stress and cognitive impairment in hepatic encephalopathy following bile duct ligation.
abstract: Oxidative stress caused by ammonia toxicity is known to play a key role in the pathogenesis of hepatic encephalopathy (HE). The present study was designed to evaluate the protective effect of N-acetyl-L-cysteine (NAC) supplementation in a bile duct ligation (BDL)-induced model of HE. Three weeks after BDL, rats developed biliary fibrosis which was supported by liver function tests, ammonia levels, and hydroxyproline content. Impaired cognitive and motor functions were observed along with decreased acetylcholinesterase activity in the brain of BDL rats. Cerebral cortex and cerebellum of BDL animals showed an increase in lipid peroxidation and reduction in total and nonprotein thiols along with reduction in antioxidant enzymes. Histopathological examination of cortex and cerebellum of BDL rats showed astrocytic swelling, inflammation, necrosis, and white matter edema. One week after BDL surgery, animals administered with NAC at a daily dose 100 mg/kg for 2 weeks showed significant improvement in the activity of liver marker enzymes and restored structural morphology of liver. NAC was able to ameliorate spatial memory and motor coordination deficits observed in BDL rats. NAC supplementation decreased lipid peroxidation and was also able to restore the activity of antioxidant enzymes as well as structural deficits observed in the cortex and cerebellum of BDL animals. The results clearly demonstrate that the protective effect of NAC in an experimental model of HE is mediated through attenuation of oxidative stress, suggesting a therapeutic role for NAC in individuals withHE.
authors.affiliation: Department of Biochemistry, Basic Medical Science Building, Panjab University, Chandigarh, 160014, India.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Dhanda
authors.forename: Simranjit
authors.initials: S
authors.lastname: Kaur
authors.forename: Rajat
authors.initials: R
authors.lastname: Sandhir
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001652:Bile Ducts / Q000601:surgery*; D003072:Cognition Disorders / Q000150:complications* / Q000188:drug therapy*; D006501:Hepatic Encephalopathy / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000111:Acetylcysteine