1-(8-Methoxy-4,8-dimethylnonyl)-4-(1-methyl-ethyl)benzene (MV-678): a reversible inducer of rat hepatic microsomal drug metabolism.
MV-678 [1-(8-methoxy-4,8-dimethynonyl)-4-(1-methylethyl)benzene], a recently developed insect growth regulator, increased the hepatic cytochrome P-450-dependent monooxygenase enzymes that metabolize endogenous and exogenous chemicals. In an initial set of experiments, male and female rats received 0, 50, or 800 mg/kg X d of MV-678 by gavage for 3 d, and in a second set of experiments, male rats received 0, 50, or 800 mg/kg X d of MV-678 by gavage for 30 d. A significant increase in both absolute and relative liver weight, microsomal protein content, cytochrome P-450 content, NADPH-cytochrome P-450 reductase activity, and ethylmorphine N-demethylase activity was observed in male and female rats at the high dose level at 3 d. Similar increases were observed in the 800-mg/kg X d males at 30 d. Hepatocellular hypertrophy and proliferation of endoplasmic reticulum observed at both 3 and 30 d correspond to and was consistent with microsomal enzyme induction. Reversibility of both induction and changes in morphology was determined by measuring the same parameters in animals treated for 30 d after a 15- or 30-d recovery period. At 15 d recovery, all biochemical parameters at the high dose level, except relative liver weight and microsomal ethylmorphine N-demethylase activity, had returned to control levels. No significant differences between the control and high dose group animals were noted at 30 d recovery. The hepatocellular changes observed in the high-dose group at 30 d were less apparent at 15 d recovery, and absent at 30 d recovery.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D005037:Ethylmorphine-N-Demethylase / Q000096:biosynthesis; D005260:Female; D008099:Liver / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009929:Organ Size / Q000187:drug effects; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013729:Terpenes / Q000494:pharmacology*; D013997:Time Factors
D013729:Terpenes; C023774:AI 3-36206; D003577:Cytochrome P-450 Enzyme System; D005037:Ethylmorphine-N-Demethylase; D010634:Phenobarbital