Intestinal phase II detoxification systems: effect of low-protein diet in weanling rats

The effect of a low-protein diet (6% protein, LPD) in vivo on the in vitro activities of cytosolic and microsomal glutathione S-transferase (GST-c, GST-m) and microsomal UDP-glucuronyltransferase (UDP-GT) was studied in small intestine and liver of weanling male Wistar rats. LPD interrupted the normal curve of growth of the animals, which returned to control values after refeeding with a normal diet (27% protein, ND). Hepatic and intestinal GST-c increased in control rats in parallel with the growth curve. The microsomal enzymes did not show growth variations, except for intestinal UDP-GT activity which began to increase from the second day of ND. After 7 days of LPD there was an increase in GST-c (liver 35%, P less than 0.05; intestine 152%, P less than 0.01) and of UDP-GT (liver 58%, intestine 178%, P less than 0.05) which returned to control values after 2 days of refeeding with ND. GST-m did not show any variations in liver or intestine. The increase in GST-c, but not in GST-m, with nutritional stress suggests preferential induction of cytosolic enzymes in those enzymatic systems which are located in both positions. The increase in such enzymes after protein malnutrition could indicate an adaptive response by detoxification mechanisms, enhancing intestinal over hepatic capacity, perhaps because the intestine is the primary route of access for orally ingested xenobiotics.