N-acetylcysteine potentially affects hepatic glutathione synthesis only under conditions of enhanced oxidative stress

ABSTRACT

N-acetylcysteine [NAC] has been widely investigated as a potentially useful protective and antioxidant agent in many pathological states. The present work was undertaken to further investigate the mechanisms of its protective effect in rats subjected to acute carbon tetrachloride [CCI4]-induced liver injury regarding its potential impact on hepatic glutathione stores. Four groups of rats have been employed; normal control, NAC-treated [40 mg/kg, i.p.], CCI4-intoxicated [0.5 ml/kg, i.p.] and NAC pretreated + CCI4-intoxicated group. Exposure to CCI4depleted reduced glutathione content and enhanced lipid peroxidation in liver tissue. However, total hepatic glutathione content was unchanged. This oxidative injury was accompanied by pronounced hepatolysis observed as an increase in serum alanine transaminase [ALT] and aspartate transaminase [AST] activities as well as total bilirubin level. Pretreatment with NAC reduced oxidative damage of liver cells as observed by decreased membrane lipid peroxidation and increased reduced glutathione content in both normal and CCI4-intoxicated groups. However, total glutathione content was only elevated in the CCI4-intoxicated group and was accompanied by a significant decrease of the elevated serum ALT and AST activities as well as bilirubin level. Thus, beside its potential direct radical-scavenging properties and reduced glutathione-sparing effect, parenterally administered NAC can replenish glutathione stores, an action that is observed only under conditions of oxidative stress