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 supplementation during water deprivation. Deprivation of water intake, which reduced food intake, resulted in no significant change in the cytochrome P-450 1A2, 2B1/2, 2C11 and 3A1/2 expression. Cytochrome P-450 2E1, however, was three-fold induced with an increase in the mRNA. Rehydration of 48-h water-deprived rats for the next 24 h with free access to foods restored the P-450 2E1 level to that of the control, although rehydration with 20% food supply failed to normalize the P-450 2E1 expression. Water deprivation caused a reduction in the plasma insulin level, which was prevented by rehydration with a sufficient food supply. The plasma insulin level was inversely related to the P-450 2E1 expression. Glucose feeding instead of foods during dehydration prevented P-450 2E1 induction in the absence of recovering the plasma insulin level. Western blot analysis revealed that the hepatic rGSTA2 level was 30% decreased in dehydrated rats, whereas the rGSTA3, M1 and M2 expression was not affected. Suppression of rGSTA2 accompanied a reduction in the mRNA. Glucose feeding further reduced rGSTA2 expression. The data indicated that expression of major P-450s and glutathione S-transferases, 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 from the reduction in food intake but not from dehydration per se. Glucose supplementation restored P-450 2E1 expression but further suppressed rGSTA2 expression during water deprivation.
Kim
S G
SG
College of Pharmacy, Seoul National University, Seoul 151-742, South Korea. sgk@snu.ac.kr
Kim
E J
EJ
Kim
Y G
YG
Lee
M G
MG
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003681:Dehydration; D004032:Diet; D005947:Glucose / Q000008:administration & dosage* / Q000494:pharmacology; D005982:Glutathione Transferase / Q000096:biosynthesis*; D015151:Immunoblotting; D008099:Liver / Q000201:enzymology*; D010599:Pharmacokinetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D014868:Water Deprivation
D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase; D005947:Glucose