N-acetylcysteine protects epithelial cells against the oxidative imbalancedue to Clostridium difficile toxins

Toxins A and B from the anaerobic bacterium Clostridium difficile are the c ausative agents of the antibiotic-associated pseudomembraneous colitis. At the subcellular level, they inhibit the Rho family GTPases, thus causing al terations of the actin cytoskeleton. The cytoskeletal integrity is also con trolled by the redox state of cells. Therefore, we hare evaluated whether a n oxidative imbalance could be involved in the toxin-induced cytopathic eff ects. Our results indicate that both toxins induce oxidative stress with a significant depletion of protein SH-groups. These responses and the cytoske leton-dependent cell retraction and rounding are significantly counteracted by N-acetylcysteine but not by alpha-tocopherol, Our study provides the fi rst evidence that the thiol supplier N-acetylcysteine impairs the cellular intoxication by acting on the cytoskeleton integrity. This also suggests a possible beneficial role for this drug during therapeutic intervention. (C) 1999 Federation of European Biochemical Societies.