N-acetylcysteine protects epithelial cells against the oxidative imbalance due to Clostridium difficile toxins.
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 alpha-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.
Department of Ultrastructures, Istituto Superiore di Sanità, Rome, Italy. carla.fiorentini@iss.it
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Fiorentini
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Falzano
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Rivabene
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Fabbri
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Malorni
D000111:Acetylcysteine / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000633:toxicity*; D002839:Chromans / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects; D004768:Enterotoxins / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D002839:Chromans; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile; D014810:Vitamin E; D005978:Glutathione; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D000111:Acetylcysteine