Role of glutathione in the toxicity of the sesquiterpene lactones hymenoxon and helenalin.

Journal of Toxicology and Environmental Health
J C MerrillM A Hayes


Hymenoxon and helenalin are toxic sesquiterpene lactones present in the toxic range plants Hymenoxys odorata and Helenium microcephalum. Helenalin (25 mg/kg) or hymenoxon (30 mg/kg) administered to immature male ICR mice caused a rapid decrease in hepatic glutathione levels and were lethally toxic to greater than 60% of the animals within 6 d. L-2-Oxothiazolidine 4-carboxylate (OTC), a compound that elevates cellular glutathione levels, administered to mice 6 or 12 h before either helenalin or hymenoxon protected against hepatic glutathione depletion and the lethal toxicity of these toxins. OTC administered at the same time as the sesquiterpene lactones was not protective, suggesting that the critical events against which glutathione is protective occur within the first 6 h. In primary rat hepatocyte cultures, hymenoxon and helenalin (4-16 microM) caused a rapid lethal injury as determined by the release of lactate dehydrogenase. Cotreatment of cultures with N-acetylcysteine at high concentrations (4 mM) afforded significant protection against lethal injury by both toxins. In contrast, BCNU, which inhibits glutathione reductase, or diethylmaleate, which depletes hepatocellular glutathione, potentiated the hepatotoxicity of hele...Continue Reading


Jul 1, 1979·Journal of Agricultural and Food Chemistry·O O Fapojuwo, J A Maga
Sep 15, 1985·Biochemical Pharmacology·J MerrillS Safe
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Mar 15, 1981·Cancer·K JentzschN L Gerber
Jul 13, 1981·Life Sciences·J A HinsonJ R Gillette

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