Effects of aging and caloric restriction on hepatic drug metabolizing enzymes in the Fischer 344 rat. II: Effects on conjugating enzymes.
The effects of long-term caloric restriction on the hepatic phase II drug metabolizing enzymes were investigated in the male Fischer 344 rat. Rats that had been restricted to 60% of their pair-fed control consumption from 14 weeks post-partum exhibited altered conjugating enzyme activities at 22 months. Caloric restriction significantly reduced the age-related decrease in glutathione-S-transferase activity towards 1,2-dichloro-4-nitrobenzene, but did not significantly alter the age-related changes in UDP-glucuronyltransferase or sulfotransferase activities towards hydroxysteroids. Caloric restriction appeared to increase hepatic microsomal UDP-glucuronyltransferase activity toward bilirubin and gamma-glutamyltranspeptidase activities. These observations suggest that caloric restriction has multiple effects on the hepatic phase II drug metabolizing enzymes in the rat. Such effects may alter hepatic metabolism and activation or detoxification of drugs and carcinogens.
Leakey
J A
JA
Division of Reproductive and Developmental Toxicology, National Center for Toxicological Research, Jefferson, AR 72079.
Cunny
H C
HC
Bazare
J
J
Webb
P J
PJ
Lipscomb
J C
JC
Slikker
W
W
Feuers
R J
RJ
Duffy
P H
PH
Hart
R W
RW
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002149:Energy Intake; D004851:Epoxide Hydrolases / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism*; D008658:Inactivation, Metabolic; D008099:Liver / Q000201:enzymology*; D008297:Male; D004364:Pharmaceutical Preparations / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D015238:Sulfotransferases / Q000378:metabolism
D004364:Pharmaceutical Preparations; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D015238:Sulfotransferases; D004851:Epoxide Hydrolases