Accelerated cytotoxic mechanism screening of isoniazid and phenylhydrazine using an in vitro hepatocyte inflammation model.
Published: 2006
Language: eng
Number of pages: 72
ISBN-13: 9780494213568
Description: The use of hydrazine-derivatives as therapeutic agents is still quite prevalent despite the many documented toxic effects. In the present study we have screened various hydrazines, with a particular focus on isoniazid and phenylhydrazine, in an attempt to elucidate their molecular mechanism of toxicity. As hepatoxicity in vivo induced by many hepatotoxins has previously been attributed to resident or infiltrating inflammatory tells that form H2O2 when activated, the effect of H 2O2 on the hepatocyte cytotoxicity in WM of various hydrazines was investigated for the first time. It was found that H2O 2 markedly increased the cytotoxicity of these hydrazines, and derivatives of, by 10-100-fold. The cytotoxic mechanism for isomazid involved reactive oxygen species (ROS) formation and lipid peroxidation (LPO). The cytotoxic mechanism for phenylhydrazine involved ROS formation, LPO, GSH oxidation and collapse of the mitochondrial membrane potential, which occurred before the onset of cytotoxicity.
Notes: Source: Masters Abstracts International, Volume: 45-03, page: 1474.

Thesis (M.Sc.)--University of Toronto, 2006.

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