Characterization of t-butyl hydroperoxide toxicity in cultured rat cortical neurones and astrocytes.
The present study investigates the toxicity of t-butyl hydroperoxide (t-BuOOH) in cultured rat cortical neurones and astrocytes. Both neurones and astrocytes were destroyed by exposure to t-BuOOH in a time- and concentration-dependent manner. Astrocytes were more resistant to destruction by hydrogen peroxide (H2O2) than neurones, but there was no difference in susceptibility to t-BuOOH between neurones and astrocytes. The toxic effect of t-BuOOH was significantly blocked by antioxidants, propyl gallate and trolox, but not by superoxide dismutase nor by H2O2-scavengers, catalase and 4-nitrophenylglyoxylic acid. These results suggest that t-BuOOH toxicity is caused by oxidative stress unrelated to superoxide and H2O2. In addition, the toxic effect of t-BuOOH was attenuated by the presence of iron chelators, deferoxamine and N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine, indicating the requirement of endogenous iron for t-BuOOH toxicity.
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
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Saito
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects* / Q000473:pathology; D002374:Catalase / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D002614:Chelating Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000494:pharmacology; D007501:Iron / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology; D020122:tert-Butylhydroperoxide / Q000633:toxicity*
D000975:Antioxidants; D002614:Chelating Agents; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D020122:tert-Butylhydroperoxide; D007501:Iron; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione