Studies of anthelminthic benzimidazole derivatives on cytochrome P450 1A (CYP1A) dependent detoxification mechanism in Labeo rohita

Fenbendazole (FBZ) and Mebendazole (MBZ) are considered the most safe and potent broad spectrum anthelminthic agents used against intestinal helminthic infection in humans and animals. In the present study, the induction and expression of Cytochrome p4501A (CYP1A) was observed against the benzimidazole derivatives (FBZ and MBZ) administrated at 20 mg/kg body weight of fish (Labeo rohita). The enzymatic activity of CYP1A induction was assayed by Ethoxyresorufin-O-deethylase (EROD) method from hepatic microsomal fraction at 0, 24, 48, 72 and 96 h post drug administration. EROD analysis showed the induction of CYP1A activity from 1.9 to 3.8 with FBZ and 3.8 to 6.0 times higher with MBZ group than control. The CYP1A gene induction was found significant in all time point (p < 0.05) with highest level at 48 h in FBZ fed group, while at 72 h in case of MBZ fed group of fishes. The overall expression level was high in MBZ group in compared to FBZ administered group and control. Increase in the CYP1A induction and expression caused by MBZ may lead to the acceleration of drug elimination and thus to the loss of efficacy in compare to FBZ fed fishes which showed less induction of CYP1A. Thus, present study revealed that detoxification metabolism for FBZ in Labeo rohita is efficient as compared to MBZ. The information establishes the interaction of drugs with CYP1A gene and metabolization in fish.