Effect of sodium sulfadimethylpyrimidine on multiple forms of cytochrome P450 in chicken

Abstract

OBJECTIVE: To study the effect of sodium sulfadimethylpyrimidine (SDMP) on different forms of CYP 450 enzymes induced by phenobarbital (CYP 2B1, 2B2 and 3A), isoniazid (CYP 2E1), benzo(a)pyrene (CYP 1A1), clotrimazole (CYP 3A), and clofibrate (CYP 4A). MATERIALS AND METHODS: Chickens (Hubbard, male) weighing 250-300 g were divided into 17 groups of six each. Five experimental sets were prepared containing three subgroups each to test five different inducers. Microsomes were isolated by calcium precipitation. The levels of electron transport components, CYP 450, cytochrome b5, and cytochrome c-reductase were determined using extinction coefficients. Activities of drug-metabolizing enzymes were assayed. RESULTS: All inducers (phenobarbital, isoniazid, benzo(a)pyrene, clotrimazole, and clofibrate) showed significant induction of mixed function oxidase in chicken. The SDMP treatment of inducer-pretreated chicken caused a significant decrease in electron transport components and activities of drug-metabolizing enzymes when compared with treatment of inducer alone. Phenobarbital, isoniazid, and benzo(a)pyrene treatments of SDMP-pretreated chicken showed no significant change in induction pattern, however, significant alterations were observed in the induction pattern of clotrimazole and clofibrate. CONCLUSION : Our studies suggest that CYP 2B1, 2B2, 3A; CYP 2E1; CYP 1A1; CYP 3A and CYP 4A are susceptible species of CYP 450 to SDMP and its metabolites. The SDMP also affected in the induction pattern of some of the inducers with respect to CYP 450 isoforms.