Title
Glutathione depletion in rat hepatocytes: A mixture toxicity study with alpha,ß-unsaturated esters
Author
Freidig, A.
Hofhuis, M.
van Holstijn, I.
Hermens, J.
TNO Voeding
Publication year
2001
Abstract
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.
Subject
Nutrition
acrolein
acrylic acid
allyl compound
ester
glutathione
methacrylic acid
animal cell
article
chemical reaction
controlled study
cytotoxicity
in vitro study
liver toxicity
male
mathematical analysis
nonhuman
protein content
rat
reaction analysis
risk assessment
Acetaldehyde
Acrolein
Animals
Cell Survival
Cells, Cultured
Dose-Response Relationship, Drug
Esters
Fumarates
Glutathione
Hepatocytes
Male
Methacrylates
Models, Statistical
Rats
Rats, Wistar
Animalia
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http://resolver.tudelft.nl/uuid:a5e7910e-7866-4934-9385-2acc6def7e95
DOI
https://doi.org/10.1080/00498250110052733
TNO identifier
57058
Source
Xenobiotica, 31 (5), 295-307
Document type
article