Suzuki Tomohiro, Hirai Anri, Khidkhan Kraisiri, Nimako Collins, Ichise Takahiro, Takeda Kazuki, Mizukawa Hazuki, Nakayama Shouta M M, Nomiyama Kei, Hoshi Nobuhiko, Maeda Mizuki, Hirano Tetsushi, Sasaoka Kazuyoshi, Sasaki Noboru, Takiguchi Mitsuyoshi, Ishizuka Mayumi, Ikenaka Yoshinori
Laboratory of Toxicology, Department of Environmental Veterinary Science, Faculty of Veterinary Medicine, Hokkaido University, Kita-18 Nishi-9, Kita-ku, Sapporo 060-0818, Japan.
Laboratory of Toxicology, Department of Environmental Veterinary Science, Faculty of Veterinary Medicine, Hokkaido University, Kita-18 Nishi-9, Kita-ku, Sapporo 060-0818, Japan; Department of Pharmacology, Faculty of Veterinary Medicine, Kasetsart University, No. 50 Ngamwongwan Road, Lat Yao Subdistrict, Chatuchak District, Bangkok 10900, Thailand.
Pestic Biochem Physiol. 2021 Jun;175:104847. doi: 10.1016/j.pestbp.2021.104847. Epub 2021 Apr 3.
Fipronil is a phenylpyrazole insecticide that is widely used as a pesticide and a veterinary drug, although studies suggest that it could be toxic to mammals. The objectives of this study were to examine the pharmacokinetic profile of fipronil in mice, dogs, and cats, and to evaluate its effects on emotional and cognitive behaviors of dogs and cats using the data obtained from mice. The assessment of in vivo kinetics of fipronil was conducted in mice and dogs. We also performed behavioral tests (elevated plus-maze and Y-maze) and measured the levels of neurotransmitters in mice exposed to fipronil. In addition, the in vitro metabolism of fipronil were evaluated using liver microsomes of rats, mice, dogs, and cats. The results revealed that fipronil is distributed throughout the body (blood, brain, adipose tissue, and liver) of mice after dermal application. It was metabolized to fipronil sulfone primarily in the liver. The data on kinetics show that both fipronil and fipronil sulfone have a longer half-life in dogs and cats than in mice. The behavioral tests indicated that fipronil and fipronil sulfone could affect emotional and cognitive behaviors and alter the levels of neurotransmitters (dopamine in the striatum and serotonin in the hippocampus) in mice. Furthermore, we found that dogs and cats have a low ability to metabolize fipronil than mice and rats. However, further comprehensive studies are needed to determine whether fipronil affects the emotional and cognitive behaviors when administered to dogs and cats. To the best of our knowledge, this is the first study to examine the pharmacokinetic data and verify the effects of fipronil on emotional and cognitive behaviors of dogs and cats using the data obtained from mice.
氟虫腈是一种苯基吡唑类杀虫剂，广泛用作农药和兽药，不过研究表明它可能对哺乳动物有毒。本研究的目的是检测氟虫腈在小鼠、狗和猫体内的药代动力学特征，并利用从小鼠获得的数据评估其对狗和猫的情绪及认知行为的影响。在小鼠和狗身上进行了氟虫腈体内动力学评估。我们还对接触氟虫腈的小鼠进行了行为测试（高架十字迷宫和Y迷宫）并测量了神经递质水平。此外，利用大鼠、小鼠、狗和猫的肝微粒体评估了氟虫腈的体外代谢情况。结果显示，经皮肤给药后，氟虫腈在小鼠全身（血液、脑、脂肪组织和肝脏）分布。它主要在肝脏中代谢为氟虫腈砜。动力学数据表明，氟虫腈和氟虫腈砜在狗和猫体内的半衰期比在小鼠体内更长。行为测试表明，氟虫腈和氟虫腈砜会影响小鼠的情绪和认知行为，并改变神经递质水平（纹状体中的多巴胺和海马体中的5-羟色胺）。此外，我们发现狗和猫代谢氟虫腈的能力比小鼠和大鼠低。然而，需要进一步进行全面研究以确定氟虫腈给狗和猫用药时是否会影响其情绪和认知行为。据我们所知，这是第一项检测药代动力学数据并利用从小鼠获得的数据验证氟虫腈对狗和猫情绪及认知行为影响的研究。
