IN-VITRO INHIBITION OF CYP2B1 MONOOXYGENASE BY BETA-MYRCENE AND OTHERMONOTERPENOID COMPOUNDS

beta-myrcene (MYR) is an acyclic monoterpene found in the essential oi ls of several useful plants such as lemongrass (Cymbopogon citratus), hop, bay, verbena and others. Recently it has been reported that MYR a s well as lemongrass oil blocked the metabolic activation of some prom utagens (e.g., cyclophosphamide and aflatoxin B1) in in vitro genotoxi city assays. The present study was performed to evaluate the inhibitor y effects of MYR and some other monoterpenoid compounds on microsomal enzymes involved in the activation of genotoxic substances. The effect s of MYR and other monoterpenes on the activity of pentoxyresorufin-O- depenthylase (PROD), a selective marker for CYP2B1, was determined in a pool of liver microsomes prepared from phenobarbital-treated rats. T he effect of MYR on the activity of ethoxyresorufin-O-deethylase (EROD ), a marker for CYP4501Al, was investigated in liver microsomes of unt reated rats. Results revealed that MYR had almost no effect on EROD (I C50 > 50 mu M), but produced a concentration-dependent inhibition of P ROD activity (IC50 = 0.14 mu M). The analysis of alterations produced by MYR on PROD kinetic parameters (Lineweaver-Burk plot) suggested tha t inhibition is competitive (K-i = 0.14 mu M). The inhibitory effects of seven other monoterpenes on PROD activity (pentoxyresorufin 5 mu M) were also studied and the IC50 were as follows: (-)-alpha-pinene, 0.0 87 mu M; (+)-alpha-pinene, 0.089 mu M; d-limonene, 0.19 mu M; alpha-te rpinene, 0.76 mu M; citral, 1.19 mu M; citronellal, 1.56 mu M, and (+/ -) camphor, 7.89 mu M. The potent inhibitory effects on CYP4502B1 sugg est that MYR, and other monoterpenes, interfere with the metabolism of xenobiotics which are substrates for this isoenzyme. (C) 1997 Elsevie r Science Ireland Ltd.