Effects of D-limonene on hepatic microsomal monooxygenase activity and paracetamol-induced glutathione depletion in mouse

1. d-Limonene, a monoterpenoid constituent of citrus fruit oil, blocks tumour induction by chemical carcinogens in laboratory animals, apparently by preventing bioactivation of procarcinogens and by enhancing conjugation of proximal carcinogenic metabolites.2. Inhibitory effects of d-limonene were measured in vitro using cytochrome P450 isoform-specific substrates. d-Limonene inhibited p-nitrophenol hydroxylase (pNP) activity in vitro in liver microsomes from acetone-, phenobarbital (PB)- and β-naphthoflavone (BNF)-treated mouse, and 7-ethoxyresorufin O-deethylase (EROD) activity in microsomes from PB- and BNF-treated mouse. p-Nitrophenol and ethoxyresorufin are substrates for cytochromes P2E1 and P1A1, respectively. No inhibition of benzphetamine (BNZP) or aminopyrine (AP) demethylases by d-limonene was observed.3. EROD, BNZP and AP activities in liver microsomes were increased 18 h after i.p. administration of d-limonene to acetone-induced mouse, while pNP activity was unchanged. The immunodetectable pr...