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 (two-thirds) hepatectomy (PH) on hepatic and intestinal glutathione S-transferases (GSTs) activities. A significant decrease of cytosolic hepatic GSTs activity was observed after the PH. The lowest value of hepatic GSTs was obtained 48 h after the surgery. On the other hand, intestinal GSTs activities increased after PH, reaching the highest values 48 h after the hepatic lobes resection. The hepatic GSTs activities diminution was attributed, in part, to the high accumulation of bile acids in the liver tissue of hepatectomized rats, also demonstrated by a higher 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 affinities. Vmax(1) and Vmax(2) were lower in PH rats suggesting a non competitive inhibition mechanism. The inhibitory effect of bile acids decreased during liver regeneration process of hepatectomized rats dissapearing 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 high and low affinities) was attributed to the presence of polyamines, mainly putrescine, produced during the hepatic regeneration process. In this regard, it was showed that GABA treatment, which inhibits polyamine synthesis, completely abolished the increase on intestinal GSTs activities. Finally, the treatment with exogenous putrescine showed that in hepatectomized and sham-operated rats. the polyamine induced GSTs activities in both tissues. In PH rats, the putrescine dependent increase of hepatic GSTs was masked by the inhibitor effect of bile acids. In addition, a summation effect of endogenous and exogenous putrescine was probably the 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 the hypothetical detoxification power of the intestine during the hepatocellular insufficiency which follows a two-thirds hepatectomy.