Neutrophil- and glutathione-mediated hepatotoxicity of alpha-naphthylisothiocyanate

Drug Metab Rev. 1997 Feb-May;29(1-2):153-65. doi: 10.3109/03602539709037578.

Abstract

In summary, both glutathione and blood neutrophils contribute to ANIT hepatotoxicity. Glutathione contributes by virtue of its ability to form a reversible S-conjugate with ANIT that is critical in shuttling ANIT into bile. Where it is released in large and probably toxic concentrations. The possibility remains that this conjugate may be bioactivated by secondary mechanisms, but no evidence for a toxic glutathionyl conjugate of ANIT currently exists. Neutrophils and platelets both appear to play important roles in ANIT hepatotoxicity. The role of platelets is currently unknown, but studies in vitro raise the possibility that neutrophils may be activated during ANIT exposure to release cytotoxic proteases that cause injury to target cells. Although ANIT activates neutrophils in vitro, the mechanisms by which neutrophils are recruited into the periportal region and activated in vivo remain unknown.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • 1-Naphthylisothiocyanate / toxicity*
  • Animals
  • Chemical and Drug Induced Liver Injury / metabolism*
  • Chemical and Drug Induced Liver Injury / pathology*
  • Endotoxins / toxicity
  • Glutathione / metabolism*
  • Glutathione / physiology*
  • Neutrophils / drug effects
  • Neutrophils / physiology*

Substances

  • Endotoxins
  • 1-Naphthylisothiocyanate
  • Glutathione