Antibiotic Furazolidone Induces CYP1A But Not CYP2E1 Subfamily in Rat Liver

Abstract

ABSTRACT. 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.

Repeated Treatment with Furazolidone Induces Multiple Cytochrome P450-Related Activities in Chicken Liver, but Not in Rat Liver

“…This discrepancy may have been caused by the different method of FZ-dosing used in that study. Our results were also inconsistent with those of a previous study that showed FZ treatment in rats caused induction of CYP1A1 estimated using the Western blot analysis [32]. In contrast, treatment of chickens with 125 mg/kg of FZ was associated with a significant increase in the CYP-related activities (i.e., HXOH, APND, EROD, MROD and PNPH), except for PROD (Table 1).…”

“…AOZ administration at an equimolar dose to FZ (125 mg/kg) caused no alteration in CYP-related activities in both rats and chickens with the exception of PNPH activity. This study confirmed that FZ treatment in chicken causes induction of drug-metabolizing enzymes observed previously in rats and pigs [32, 37]. FZ may therefore induces multiple CYPs in humans and numerous animal species.…”

“…Successive oral administration of FZ was also reported to cause induction of hepatic CYP1A1 isozymes [32]. In addition, successive bolus doses of FZ in rats were shown to decrease the metabolic rate of two kinds of drugs in in vivo and increase the duration of barbital anesthesia [3].…”