Propiconazole-induced cytochrome P450 gene expression and enzymatic activities in rat and mouse liver.

Toxicol Lett

National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.

Published: February 2005

AI Article Synopsis

  • Propiconazole is a fungicide used on various crops and was studied for its impact on liver enzyme genes in rats and mice.
  • In the study, rats and mice were given propiconazole daily for 14 days, leading to significant increases in mRNA expression of specific cytochrome P450 genes, particularly at high doses.
  • The findings suggest that propiconazole activates key liver enzymes (CYP1A2, CYP2B, and CYP3A) in both species, indicating its potential effects on liver metabolism.

Article Abstract

Propiconazole is a N-substituted triazole used as a fungicide on fruits, grains, seeds, hardwoods, and conifers. In the present study, propiconazole was examined for its effects on the expression of hepatic cytochrome P450 genes and on the activities of P450 enzymes in male Sprague-Dawley rats and male CD-1 mice. Rats and mice were administered propiconazole by gavage daily for 14 days at doses of 10, 75, and 150 mg/kg body weight/day. Quantitative real time RT-PCR assays of rat hepatic RNA samples from animals treated at the 150 mg/kg body weight/day dose revealed significant mRNA overexpression of the following genes compared to control: CYP1A2 (1.62-fold), CYP2B1 (10.8-fold), CYP3A1/CYP3A23 (2.78-fold), and CYP3A2 (1.84-fold). In mouse liver, propiconazole produced mRNA overexpression of Cyp2b10 (2.39-fold) and Cyp3a11 (5.19-fold). mRNA expression of CYP1A1 was not detected in liver tissues from treated or controls animals from either species. Propiconazole significantly induced both pentoxyresorufin O-dealkylation (PROD) and methoxyresorufin O-dealkylation (MROD) activities in both rat and mouse liver at the 150 mg/kg body weight/day and 75 mg/kg body weight/day doses. In summary, these results indicated that propiconazole induced CYP1A2 in rat liver and CYP2B and CYP3A families of isoforms in rat and mouse liver.

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http://dx.doi.org/10.1016/j.toxlet.2004.10.006DOI Listing

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