IS INTESTINAL CYTOSOLIC GLUTATHIONE-S-TRANSFERASE AN ALTERNATIVE DETOXIFICATION PATHWAY IN 2 3 HEPATECTOMIZED RATS/

The present study was designed to investigate the effect of partial (t wo-thirds) hepatectomy (PH) on hepatic and intestinal glutathione S-tr ansferases (GSTs) activities. A significant decrease of cytosolic hepa tic GSTs activity was observed after the PH. The lowest value of hepat ic GSTs was obtained 48 h after the surgery. On the other hand, intest inal GSTs activities increased after PH, reaching the highest values 4 8 h after the hepatic lobes resection. The hepatic GSTs activities dim inution was attributed, in part, to the high accumulation of bile acid s in the liver tissue of hepatectomized rats, also demonstrated by a h igher retention of [C-14] taurocholate. The kinetic analysis performed with 1-chloro-2,4-dinitrobenzene (CDNB) as substrate showed two sets of parameters, indicating the presence of isozymes of high and low aff inities. Vmax(1) and Vmax(2) were lower in PH rats suggesting a non co mpetitive inhibition mechanism. The inhibitory effect of bile acids de creased during liver regeneration process of hepatectomized rats dissa pearing at 7 days after PH. Conversely, in non regenerating rats (GABA treated) the inhibitory mechanism was still observed at 7 days after the surgery. The increase of intestinal GSTs activities (isozymes of h igh and low affinities) was attributed to tile presence of polyamines, mainly putrescine, produced during tile hepatic regeneration process. In this regard, it was showed that GABA treatment, which inhibits pol yamine synthesis, completely abolished the increase on intestinal GSTs activities. Finally, the treatment with exogenous putrescine showed t hat in hepatectomized and sham-operated rats. the polyamine induced GS Ts activities in both tissues. In PH rats, the putrescine dependent in crease of hepatic GSTs was masked by the inhibitor effect of bile acid s. In addition, a summation effect of endogenous and exogenous putresc ine was probably tile reason of the induction of intestinal GSTs after PH. The GSH/GSSG ratio did not change during the treatments, as well as the microsomal GST activity of both tissues. The work points out th e hypothetical detoxification power of the intestine during the hepato cellular insufficiency which follows a two-thirds hepatectomy.