Effect of toluene and xylenes on liver glutathione and their urinary excretion as mercapturic acids in the rat |
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Authors: | R. van Doorn R. P. Bos R. M. E. Brouns Ch. -M. Leijdekkers P. Th. Henderson |
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Affiliation: | (1) Institute of Pharmacology and Toxicology, University of Nijmegen, Nijmegen, The Netherlands |
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Abstract: | Administration of toluene and xylenes to rats caused a decrease in liver glutathione concentration. The effect was most pronounced after the administration of o-xylene. 26% of the initial glutathione level was found three hours after treatment with o-xylene (4.0 mmoles/kg).No in vitro conjugation of o-xylene with glutathione was observed, neither spontaneously nor in the presence of 105,000 g supernatant from rat liver homogenate, containing glutathione S-transferases. Thus, a metabolite of o-xylene, which is not formed during incubation with 105,000 g supernatant, reacts with glutathione.A thioether was isolated from urine of rats given o-xylene; the compound was identified as o-methylbenzyl mercapturic acid by GC-MS and NMR. Chromatographic evidence was found for the presence of benzyl mercapturic acid in the urine of toluene-treated rats. The amounts of mercapturic acids excreted in the urine after administration of toluene, p-xylene, m-xylene, and o-xylene were 0.4–0.7, 0.6, 1.3, and 10–21% of the dose, respectively.These results demonstrate the involvement of a thusfar unknown pathway in the biotransformation of toluene and xylenes. |
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Keywords: | Toluene and Xylenes metabolism Glutathione Mercapturic acids |
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