In vivo and in vitro destruction of rat liver cytochrome P-450 by a monoterpene ketone, pulegone

Abstract

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 (~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.