[M-ZZ51] Environmental Pollution, Environmental Toxicology and Humans/Animals Health

[MZZ51-11] Differences in cytochrome P450-involved metabolism of fipronil in poultry

*Kraisiri Khidkhan¹, Saranya POAPOLATHEP¹, Sittinee KULPRASERTSRI¹, Rattapong SUKKHEEWAN¹, Paphatsara KHUNLERT², Shouta MM NAKAYAMA³, Amnart POAPOLATHEP¹ (1.Department of Pharmacology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand, 2.Agricultural Toxic Substance Research Group, Agricultural Production Sciences Research and Development Division, Department of Agriculture, Ministry of Agriculture and Cooperatives, 3.Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University)

Keywords:Cytochrome P450, Metabolism, Species differences

Fipronil is effective pesticide widely used in agriculture including cultivating plants and livestock. Domestic poultry is among non-target species of exposure to fipronil, however, the study on metabolic effects on fipronil exposure in avian have been limited. The objective in this study was to investigate the comparative capacity of CYP-involved metabolism of fipronil among domestic poultry. In vitro reaction mixtures between fipronil substrate and hepatic microsome of chicken, duck, quail and goose were conducted. The levels of fipronil sulfone were measured and analyzed using Michaelis-Menten equation. The reaction mixture using microsome of duck had the significantly highest maximum reaction rate (Vmax = 2,195 ± 562 pmol/min/mg protein) compared to those of other avian species (chicken: 373 ± 26 pmol/min/mg protein, quail: 271 ± 107 pmol/min/mg protein, and goose: 200 ± 35 pmol/min/mg protein). The affinities of fipronil for CYP enzymes involved in the oxidation to sulfone were significantly less in duck (Km = 568 ± 185 µM), and goose (Km = 500 ± 197 µM) than in chicken (Km = 60 ± 14 µM). The intrinsic clearance rate calculations (Vmax/Km) indicated that chicken (6.4 ± 1.1 μL/min/mg protein) and duck (4.0 ± 0.5 μL/min/mg protein) are more efficient in the CYP-mediated metabolism of fipronil to sulfone than quail (1.5 ± 0.3 μL/min/mg protein) and goose (0.42 ± 0.1 μL/min/mg protein). However, further studies on the specific CYP isoform of fipronil biotransformation, phase II metabolism, and excretion of sulfone metabolite in poultry are needed.