Expression of cytochrome P-450s and glutathione S-transferases in the rat liver during water deprivation: Effects of glucose supplementation

Pharmacokinetic profiles of therapeutic agents change in dehydrated animals . The present study was designed to determine the expression of xenobiotic- metabolizing enzymes in the rat liver and the effect of glucose supplementa tion during water deprivation. Deprivation of water intake, which reduced food intake, resulted in no sign ificant change in the cytochrome P-450 1A2, 2B1/2, 2C11 and 3A1/2 expressio n. Cytochrome P-450 2E1, however, was threefold induced with an increase in the mRNA. Rehydration of 48-h water-deprived rats for the next 24 h with f ree access to foods restored the P-450 2E1 level to that of the control, al though rehydration with 20% food supply failed to normalize the P-450 2E1 e xpression. Water deprivation caused a reduction in the plasma insulin level , which was prevented by rehydration with a sufficient food supply. The pla sma insulin level was inversely related to the P-450 2E1 expression. Glucos e feeding instead of foods during dehydration prevented P-450 2E1 induction in the absence of recovering the plasma insulin level. Western blot analys is revealed that the hepatic rGSTA2 level was 30% decreased in dehydrated r ats, whereas the rGSTA3, M1 and M2 expression was not affected. Suppression of rGSTA2 accompanied a reduction in the mRNA. Glucose feeding further red uced rGSTA2 expression. The data indicated that expression of major P-450s and glutathione S-transf erases, except P-450 2E1, was not greatly affected by water deprivation and that the P-450 2E1 induction and a decrease in plasma insulin resulted fro m the reduction in food intake but not from dehydration per se. Glucose sup plementation restored P-450 2E1 expression but further suppressed rGSTA2 ex pression during water deprivation. Copyright (C) 2001 John Wiley & Sons, Lt d.