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A General Method for Detecting Nitrosamide Formation in the In Vitro Metabolism of Nitrosamines by Cytochrome P450s
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Effect of natamycin on cytochrome P450 enzymes in rats

María Aránzazu Martínez1, María Rosa Martínez-Larrañaga, Victor Castellano

  • 1Department of Toxicology and Pharmacology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain.

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association
|September 5, 2013
PubMed

Insights

Natamycin, an antifungal food additive, significantly reduced drug-metabolizing enzyme activities in rats at higher doses. This suggests natamycin may alter the metabolism and clearance of other substances in the body.

Area of Science:

  • Food Science
  • Toxicology
  • Biochemistry

Background:

  • Natamycin is a polyene macrolide antibiotic used as a food additive to prevent mold.
  • Contradictory findings exist regarding the genotoxic effects of macrolides, raising human safety concerns.

Purpose of the Study:

  • To investigate the in vivo effects of natamycin on drug-metabolizing enzyme activities in rat liver microsomes.
  • To determine the dose-dependent impact of natamycin on specific cytochrome P450 (CYP) enzymes.

Main Methods:

  • Rats were orally administered natamycin at doses of 0.3, 1, 3, and 10 mg/kg body weight daily for six days.
  • Hepatic microsomes were isolated from treated rats to determine the activities of CYP2E1, CYP1A1/2, CYP2B1/2, and CYP4A1/2 enzymes.

Main Results:

  • Natamycin treatment significantly decreased the activities of CYP2E1, CYP1A1/2, CYP2B1/2, and CYP4A1/2 enzymes in a dose-dependent manner at doses of 1, 3, and 10 mg/kg.
  • No significant effect on these enzyme activities was observed at the lowest dose of 0.3 mg/kg.

Conclusions:

  • Natamycin administration may not enhance xenobiotic toxicity through metabolic activation or reactive metabolite accumulation.
  • The findings suggest natamycin could influence the clearance of xenobiotics metabolized by the studied CYP enzymes.
Keywords:
Cytochrome P450 enzymesHepatic microsomesNatamycinRats

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