Glutathione depletion in rat hepatocytes : a mixture toxicity study with alpha,ß-unsaturated esters
| Autor: | Freidig, A., Hofhuis, M., Holstijn, I. van, Hermens, J. |
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| Přispěvatelé: | TNO Voeding |
| Rok vydání: | 2001 |
| Předmět: |
chemical reaction
Male methacrylic acid in vitro study Cell Survival animal cell Acetaldehyde mathematical analysis Fumarates Animals Animalia controlled study rat glutathione Acrolein Rats Wistar allyl compound Cells Cultured Nutrition nonhuman Models Statistical Dose-Response Relationship Drug acrylic acid article risk assessment Esters protein content liver toxicity Rats reaction analysis Hepatocytes cytotoxicity Methacrylates ester |
| Zdroj: | Xenobiotica, 5, 31, 295-307 |
| Popis: | Glutathione (GSH) depletion is often reported as an early cytotoxic effect, caused by many reactive organic chemicals. In the present study, GSH depletion in primary rat hepatocytes was used as an in vitro effect-equivalent to measure the toxic potency of α,β-unsaturated esters (acrylates and methacrylates). 2. When these compounds were administered as a mixture, GSH depletion was dose additive. The result of the mixture study shows that GSH depletion may be a useful effect-equivalent for the risk assessment of mixtures of α,β-unsaturated esters. 3. To get more insight in the underlying mechanisms of GSH depletion, the metabolism of two esters was investigated in greater detail. One of them, allyl methacrylate, was metabolized to acrolein. This metabolic pathway can explain the high potency of allyl methacrylate to deplete GSH despite its low intrinsic chemical reactivity. |
| Databáze: | OpenAIRE |
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