The major metabolite of aflatoxin B1 in the rat is a glutathione conjugate

Chemico-biological Interactions
G H Degen, H G Neumann

Abstract

[14C]aflatoxin B1 (AFB1) was injected i.p. into female Wistar rats. Half of the dose was eliminated into the bile mostly as polar non-extractable metabolites. Among these a glutathione conjugate was the main component. The same conjugate was formed when rat liver postmitochondrial supernatant was incubated with AFB1 and [3H]glutathione. The conjugate was purified by ion exchange chromatography, gel-filtration and thin layer chromatography (TLC). It was tentatively identified as 2,3-dihydro-2-(S-glutathionyl)-3-hydroxy aflatoxin B1 (AFB1-GSH-conjugate). This structure was derived mainly from amino acid analysis, ultraviolet spectra and the enzymatic requirements for its formation in in vitro experiments. In the rat this detoxification product of the potentially ultimate reactive AFB1-epoxide constitutes about 10% of the administered dose and thus underlines the quantitative importance of this activating pathway.

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