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Effects of dithiocarb and (+)-catechin on the glutathione-conjugating system in rat liver cytosol in vivo and in vitro

1982; Academic Press; Volume: 14; Issue: 9 Linguagem: Inglês

10.1016/s0031-6989(82)80002-7

1879-2936

Mamoun Younes, J. Larseille, C.‐P. Siegers,

Genomics, phytochemicals, and oxidative stress

The effects of (+)-catechin (CAT) and dithiocarb (DTC) on the glutathione-conjugating system of rat liver were investigated after a single dose as well as after repeated treatment for 7 and for 28 days. The hepatic levels of reduced glutathione (GSH) remained unaffected in all cases. Both agents exerted a significant reduction of the glutathione S-transferase activity towards an epoxide substrate (1,2-epoxy-3-(p-nitrophenoxy) propane, ENPP) following the application of a single dose (200 mg/kg p.o.). Seven-days treatment with either agent had no effect, whereas the treatment for 28 days evoked a dose-dependent inhibition of the epoxide transferase activity. The GSH S-transferase activity towards an aryl substrate (1-chloro-2,4-dinitrobenzene, CDNB) was depressed only after treatment with (+)-catechin for seven days or for four weeks. In vitro studies revealed for the aryl transferase activity an inhibition by DTC being of the competitive type with respect to GSH and of the non-competitive type with respect to CDNB. Mixed-type inhibition was found with CAT with respect to either substrate. As for the epoxide transferase activity DTC exerted a mixed-type inhibition with respect to GSH and a competitive type inhibition with respect to ENPP. CAT was inhibitory only with respect to GSH giving rise to a non-competitive type inhibition. Apparant KI-values lay between 0.3 and 1 mmol/1.