Interaction of the mycotoxin penicillic acid with glutathione and rat liver glutathione S-transferases.

The in vitro interaction of the mycotoxin penicillic acid (PA) with rat liver glutathione S-transferase (GST) was studied using reduced glutathione and 1-chloro-2,4-dinitrobenzene as substrates. The inhibition of the GST activity by PA in crude extracts was dose dependent. Each of the different GST isoenzymes was inhibited, albeit at different degrees. Kinetic studies never revealed competitive inhibition kinetics. The conjugation of PA with GSH occurred spontaneously; it was not enzymatically catalyzed by GST, indicating that an epoxide intermediate is not involved in conjugation. The direct binding of PA to GST provides an additional detoxication mechanism.