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 cvt. P-450 to the extent of 32 and 76% at the end of 24 and 96 hrs respectively. However, cyt. $b_5$ and NAD(P)H-cyt. c reductase activities remained unchanged. In vitro incubation T15 min) of liver microsomes from phenobarbital mtreated rats with pulegone (10 mM), aerobically or anaerobically resulted in the loss (\sim 60%) of cyt. P-450 in the presence or absence of NADPH. Destruction of cyt. P-450 was more in PBtreated 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 mNLa nd follows first order kinetics