Glucocorticoid induction of hepatic acetyl CoA:arylamine N-acetyltransferase activity in the rat.
N-Acetylation, which is catalyzed by the enzymes N-acetyltransferase (NAT), is an important biotransformation pathway for the elimination of a wide variety of xenobiotics. Based on reports by several investigators that hydrocortisone (HYD) pretreatment increases N-acetylation in the rabbit, we examined the potential of glucocorticoids to induce NAT in the rat. Rats received pretreatment with relatively equipotent doses of HYD, prednisolone (PRED) or dexamethasone (DEX) for 5 or 10 days. Livers were removed 24 hr after the last dose and NAT activity was determined by measuring the formation of N-acetylprocainamide in cytosolic incubations in the presence of 0.42 mM acetyl CoA. All three glucocorticoids were found to cause a modest induction of NAT activity towards procainamide after dosing for 10 days. When normalized to cytosolic protein content, the potency of induction was PRED > DEX > HYD (30, 29 and 18% increase, respectively), while normalization to liver weight demonstrated equipotent NAT induction by the three agents (40%). These data indicate that glucocorticoids are capable of producing a modest induction of NAT activity in the rat.
Zaher
H
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Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, Wayne State University, Detroit, Michigan 48202.
Svensson
C K
CK
D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000096:biosynthesis*; D001835:Body Weight / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D006854:Hydrocortisone / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003907:Dexamethasone; D011239:Prednisolone; D001191:Arylamine N-Acetyltransferase; D006854:Hydrocortisone