N‐Acetylcysteine protects epithelial cells against the oxidative imbalance due to Clostridium difficile toxins

FEBS Letters

Rivabene, R.¹  Falzano, L.²  Fiorentini, C.²  Malorni, W.²  Fabbri, A.² 

[1] Department of Metabolism and Pathological Biochemistry, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy;Department of Ultrastructures, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy

关键词: Oxidative alteration;    N-Acetylcysteine;    SH-group;    Cytoskeleton;    Clostridium difficile;    Toxin;   

DOI  :  10.1016/S0014-5793(99)00706-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Toxins A and B from the anaerobic bacterium Clostridium difficile are the causative agents of the antibiotic-associated pseudomembraneous colitis. At the subcellular level, they inhibit the Rho family GTPases, thus causing alterations of the actin cytoskeleton. The cytoskeletal integrity is also controlled by the redox state of cells. Therefore, we have evaluated whether an oxidative imbalance could be involved in the toxin-induced cytopathic effects. Our results indicate that both toxins induce oxidative stress with a significant depletion of protein SH-groups. These responses and the cytoskeleton-dependent cell retraction and rounding are significantly counteracted by N-acetylcysteine but not by α-tocopherol. Our study provides the first 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.

【 授权许可】

Unknown