In vivo and in vitro destruction of rat liver cytochrome P-450 by a monoterpene ketone, pulegone.
In vivo administration of pulegone once daily decreased the levels of liver microsomal cyt. P-450 to the extent of 32 and 76% at the end of 24 and 96 hrs respectively. However, cyt. b5 and NAD(P)H-cyt. c reductase activities remained unchanged. In vitro incubation (15 min) of liver microsomes from phenobarbitol (PB)-treated rats with pulegone (10 mM), aerobically or anaerobically resulted in the loss (approximately 60%) of cyt. P-450 in the presence or absence of NADPH. Destruction of cyt. P-450 was more in PB-treated microsomes as compared to 3-methylcholanthrene (MC)-treated and control microsomes. The loss of cyt. P-450 was accompanied by a concomitant loss of microsomal heme. In contrast, menthone or carvone upon incubation with PB-induced microsomes resulted in the conversion (25-40%) of cyt. P-450 to cyt. P-420 without any loss of microsomal heme. The destructive process is irreversible, time dependent, linear upto a substrate concentration of 10 mM and follows first order kinetics.
D000284:Administration, Oral; D000818:Animals; D000081005:Cyclohexane Monoterpenes; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008610:Menthol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D039821:Monoterpenes; D009249:NADP / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D013997:Time Factors
D000081005:Cyclohexane Monoterpenes; D039821:Monoterpenes; D008610:Menthol; C039648:pulegone; D009249:NADP; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital