Characteristics of metabolism towards acetamiprid on musk shrew (Suncus murinus)

<p>Neonicotinoid insecticides (NNIs) are one of the most abundantly used insecticides all over the world these days. For the present risk assessment of NNIs-induced toxicities, experimental animals such as mice, rats, and rabbits have been used. However, these experimental animals are taxonomically distant from many wild mammals, and not appropriate as animal model. Thus, we focused on musk shrew (Suncus murinus) as a novel animal model. Musk shrew is classified within Euarchontoglires as other many wild mammalian species. Because of high carnivorousness, musk shrew is possible to have different metabolic characteristics from experimental animals. The objective of this study is to reveal the characteristics of metabolism towards acetamiprid (ACP), one of NNIs on musk shrew. Pharmacokinetics analysis, in vitro metabolic assay, and genetic analysis of cytochrome P450 (CYP) were performed using musk shrews, mice, and rats. As a results of pharmacokinetic analysis, concentration of ACP in blood decreased more quickly in musk shrews than mice. By in vitro metabolic assay, it was suggested that musk shrews have higher metabolic abilities towards ACP compared to mice and rats. By genetic analysis, some of CYP2A and CYP3A isoforms of musk shrews were thought to be particularly important in ACP metabolism. From the results above, unique metabolic characteristics of musk shrews were indicated. To elucidate the characteristics of CYP-dependent metabolism of xenobiotics in musk shrews, it is expected to reveal the function of each CYP isoform using recombinant CYP enzymes in the future.</p>