Antioxidant enzyme status in biliary obstructed rats: effects of N-acetylcysteine.

Background/aims: N-acetylcysteine (NAC) is a modulator of thiol levels that protects against hepatotoxic agents. The aim of this study was to investigate whether NAC might improve hepatic antioxidant defenses in chronically biliary obstructed rats.

Methods: Secondary biliary cirrhosis was induced by 28 days of bile-duct obstruction. Groups of control and cirrhotic animals received NAC (50 mumol .kg-1.d-1 i.m.) through the experimental period.

Results: Bile-duct obstruction resulted in decreased liver glutathione concentrations. Dichlorofluorescein (DCF) and thiobarbituric acid reactive substances (TBARS) concentrations, measured as markers of production of reactive oxygen species and lipid peroxidation, respectively, were significantly increased. Microsomal and mitochondrial membrane fluidity and the activities of catalase, cytosolic and mitochondrial superoxide dismutase (SOD), glutathione S-transferase, and cytosolic and mitochondrial Se-dependent and Se-independent glutathione peroxidase (GPx) were significantly reduced. NAC corrected the reduction in glutathione concentration and partially prevented the increases in DCF and TBARS concentrations. In addition, NAC treatment resulted in significant preservation of membrane fluidity and of the activities of catalase, mitochondrial SOD and the different forms of GPx.

Conclusions: Our data indicate that NAC maintains antioxidant defenses in biliary obstructed rats. These effects of NAC suggest that it may be a useful agent to preserve liver function in patients with biliary obstruction.