Induction of hepatic microsomal cytochrome P450 by dexamethasone in rhesus monkey (Macaca mulatta).
Intraperitoneal administration of 150 mg dexamethasone (DEX) Kg-1 body wt for four days to rhesus monkeys resulted in statistically significant increases in the activities of hepatic tyrosine aminotransferase (3 fold), microsomal cytochrome P450 (2 fold) and erythromycin N-demethylase (4 fold), but no change in the activities of aminopyrine N-demethylase and NADPH cytochrome c reductase. Three peaks were obtained from control or DEX-treated monkey livers on fractionation of detergent solubilized microsomes by anion exchange chromatography on DE-52. Peak II obtained from DEX-treated monkey microsomes on DE-52 demonstrated the highest specific activity of cytochrome P450 (5.84 nmol mg-1 protein) as compared to other peaks from the same microsomes or any of the peaks obtained from the control microsomes. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of the microsomes from control and experimental animals and peak II obtained after anion exchange chromatography of DEX-treated microsomes demonstrated the intensification of two polypeptides of 52.5 and 50 kDa. The results indicate that DEX is an inducer of cytochrome P450 and dependent erythromycin N-demethylase in non-human primate, Macaca mulatta.
Ojha
V
V
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Kohli
K K
KK
D000633:Aminopyrine N-Demethylase / Q000096:biosynthesis / Q000302:isolation & purification; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D002848:Chromatography, DEAE-Cellulose; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000302:isolation & purification; D003907:Dexamethasone / Q000494:pharmacology*; D004790:Enzyme Induction; D007700:Kinetics; D008253:Macaca mulatta; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000096:biosynthesis / Q000302:isolation & purification; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis / Q000302:isolation & purification; D012016:Reference Values; D014444:Tyrosine Transaminase / Q000096:biosynthesis / Q000302:isolation & purification
D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D000633:Aminopyrine N-Demethylase; D009251:NADPH-Ferrihemoprotein Reductase; D014444:Tyrosine Transaminase