title: Effect of natamycin on cytochrome P450 enzymes in rats.
abstract: Natamycin is a polyene macrolide antibiotic widely used in the food industry as a feed additive to prevent mold contamination of foods. There are many contradictory results on the genotoxic effects of macrolides which could suggest a potential risk for humans. In the present study, the effects of natamycin on the activities of some drug metabolizing enzymes in rat liver microsomes were determined in vivo. Rats were treated orally with natamycin at doses of 0.3, 1, 3 and 10 mg/kg body weight (bw)/day for 6 days. Determinations of cytochrome P450 (CYP) enzyme activities were carried out in hepatic microsomes isolated from rats treated. The activities of CYP2E1, CYP1A1/2 CYP2B1/2 and CYP4A1/2 enzymes significantly decreased after treatment with 1, 3 and 10 mg/kg bw/day, in a dose-dependent manner as compared to control. This effect was not observed after natamycin treatment at dose of 0.3 mg/kg bw/day. Our results suggest that natamycin may not potentiate the toxicity of many xenobiotics via metabolic activation and/or accumulation of reactive metabolites but also might affect the clearance of other xenobiotics detoxified by the studied CYP enzymes.
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: María Aránzazu
authors.initials: MA
authors.lastname: Martínez
authors.forename: María Rosa
authors.initials: MR
authors.lastname: Martínez-Larrañaga
authors.forename: Victor
authors.initials: V
authors.lastname: Castellano
authors.forename: Marta
authors.initials: M
authors.lastname: Martínez
authors.forename: Irma
authors.initials: I
authors.lastname: Ares
authors.forename: Alejandro
authors.initials: A
authors.lastname: Romero
authors.forename: Arturo
authors.initials: A
authors.lastname: Anadón
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D065691:Cytochrome P-450 CYP2E1 Inhibitors / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003580:Cytochromes / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008658:Inactivation, Metabolic; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D010866:Natamycin / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D017208:Rats, Wistar; D013250:Steroid Hydroxylases / Q000378:metabolism
chemical_list: D065691:Cytochrome P-450 CYP2E1 Inhibitors; D003580:Cytochromes; D010866:Natamycin; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; C017170:Cyp1a2 protein, rat; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D019362:Cytochrome P-450 CYP2B1; C025619:steroid 16-beta-hydroxylase; C465388:cytochrome P-450 CYP4A2 (rat)
keywords: Cytochrome P450 enzymes; Hepatic microsomes; Natamycin; Rats