Antibiotic furazolidone induces CYP1A but not CYP2E1 subfamily in rat liver.
Furazolidone (FZ), one of the nitrofuran fungicides, is used as a veterinary medicine in the Middle and Far Eastern countries. In this study, FZ (125 mg/kg) was administered orally to Wistar rats for 3 days. Results of the Ames test using the S-9 fraction of rats treated with FZ showed a significant increase in the number of revertant colonies. Western blot analysis of hepatic CYP isozymes induced by FZ, revealed a remarkable induction of CYP1A1 apoprotein, but CYP1A2 and CYP2E1 apoproteins were not altered. In addition, the expression of CYP1A1 mRNA level in rats treated with FZ by RT-PCR was significantly enhanced by FZ treatment. We concluded that FZ is apparently mutagenic and induces transcription of the CYP1A1 isozyme, which metabolically activates numerous promutagens, in hepatocytes.
Sasaki
Nobuo
N
Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
Sakai
Noriaki
N
Ikenaka
Yoshinori
Y
Kamiya
Tomomi
T
Heewon
Min
M
Sakamoto
Kentaro Q
KQ
Ishizuka
Mayumi
M
Fujita
Shoichi
S
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015153:Blotting, Western; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005664:Furazolidone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000900:Anti-Bacterial Agents; D007527:Isoenzymes; D005664:Furazolidone; D019363:Cytochrome P-450 CYP1A1