In vitro inhibition of CYP2B1 monooxygenase by beta-myrcene and other monoterpenoid compounds.
beta-myrcene (MYR) is an acyclic monoterpene found in the essential oils of several useful plants such as lemongrass (Cymbopogon citratus), hop, bay, verbena and others. Recently it has been reported that MYR as well as lemongrass oil blocked the metabolic activation of some promutagens (e.g., cyclophosphamide and aflatoxin B1) in in vitro genotoxicity assays. The present study was performed to evaluate the inhibitory effects of MYR and some other monoterpenoid compounds on microsomal enzymes involved in the activation of genotoxic substances. The effects 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. The effect of MYR on the activity of ethoxyresorufin-O-deethylase (EROD), a marker for CYP4501A1, was investigated in liver microsomes of untreated rats. Results revealed that MYR had almost no effect on EROD (IC50 > 50 microM), but produced a concentration-dependent inhibition of PROD activity (IC50 =0.14 microM). The analysis of alterations produced by MYR on PROD kinetic parameters (Lineweaver-Burk plot) suggested that inhibition is competitive (Ki = 0.14 microM). The inhibitory effects of seven other monoterpenes on PROD activity (pentoxyresorufin 5 microM) were also studied and the IC50 were as follows: (-)-alpha-pinene, 0.087 microM; (+)-alpha-pinene, 0.089 microM; d-limonene, 0.19 microM; alpha-terpinene, 0.76 microM; citral, 1.19 microM; citronellal, 1.56 microM, and (+/-) camphor, 7.89 microM. The potent inhibitory effects on CYP4502B1 suggest that MYR, and other monoterpenes, interfere with the metabolism of xenobiotics which are substrates for this isoenzyme.
De-Oliveira
A C
AC
Department of Biological Sciences, The National School for Public Health, Oswaldo Cruz foundation, Rio de Janeiro, Brazil.
Ribeiro-Pinto
L F
LF
Paumgartten
J R
JR
D000080462:Acyclic Monoterpenes; D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors; D005260:Female; D005503:Food Additives / Q000494:pharmacology*; D007700:Kinetics; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D039821:Monoterpenes; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000494:pharmacology*
D000080462:Acyclic Monoterpenes; D004791:Enzyme Inhibitors; D005503:Food Additives; D039821:Monoterpenes; D013729:Terpenes; C008574:beta-myrcene; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1