Effect of N-acetyl-L-cysteine on sepsis in mice

Abstract

The effect of the antioxidant $\text{N-}\text{acetyl-}\text{L}\text{-cysteine}$ was studied in a model of polymicrobial sepsis induced in CD-1 mice by cecal ligation and puncture. $\text{N-}\text{acetyl-}\text{L}\text{-cysteine}$ significantly improved survival during the 6 days following sepsis induction and caused lower liver toxicity. This effect was not related to free radicals generated by xanthine oxidase which was significantly induced in liver after cecal ligation and puncture. A specific inhibitor of xanthine oxidase, allopurinol, significantly reduced this enzyme and reduced the early survival rate. The effect of $\text{N-}\text{acetyl-}\text{L}\text{-cysteine}$ was not related either to a reduction in tumor necrosis factor production or to a modulation of nitrites or to liver glutathione content. These results show that the induction of xanthine oxidase is not deleterious in this model of sepsis and suggest that $\text{N-}\text{acetyl-}\text{L}\text{-cysteine}$ works as a direct antioxidant and scavenger of free radicals generated from other sources.