Department of Biochemistry and Microbiology, Rutgers, The State University of New Jersey, New Brunswick, New Jersey 08901, USA.
Toxicol Sci. 2010 Jan;113(1):177-86. doi: 10.1093/toxsci/kfp258. Epub 2009 Oct 27.
Pyrethroid insecticides are one of the most commonly used residential and agricultural insecticides. Based on the increased use of pyrethroids and recent studies showing that pregnant women and children are exposed to pyrethroids, there are concerns over the potential for developmental neurotoxicity. However, there have been relatively few studies on the developmental neurotoxicity of pyrethroids. In this study, we sought to investigate the developmental toxicity of six common pyrethroids, three type I compounds (permethrin, resmethrin, and bifenthrin) and three type II compounds (deltamethrin, cypermethrin, and lambda-cyhalothrin), and to determine whether zebrafish embryos may be an appropriate model for studying the developmental neurotoxicity of pyrethroids. Exposure of zebrafish embryos to pyrethroids caused a dose-dependent increase in mortality and pericardial edema, with type II compounds being the most potent. At doses approaching the LC(50), permethrin and deltamethrin caused craniofacial abnormalities. These findings are consistent with mammalian studies demonstrating that pyrethroids are mildly teratogenic at very high doses. However, at lower doses, body axis curvature and spasms were observed, which were reminiscent of the classic syndromes observed with pyrethroid toxicity. Treatment with diazepam ameliorated the spasms, while treatment with the sodium channel antagonist MS-222 ameliorated both spasms and body curvature, suggesting that pyrethroid-induced neurotoxicity is similar in zebrafish and mammals. Taken in concert, these data suggest that zebrafish may be an appropriate alternative model to study the mechanism(s) responsible for the developmental neurotoxicity of pyrethroid insecticides and aid in identification of compounds that should be further tested in mammalian systems.
拟除虫菊酯类杀虫剂是最常用的住宅和农业杀虫剂之一。基于拟除虫菊酯类的使用增加，以及最近的研究表明孕妇和儿童接触到拟除虫菊酯类，人们担心其可能具有发育神经毒性。然而，关于拟除虫菊酯类的发育神经毒性的研究相对较少。在这项研究中，我们试图研究六种常见的拟除虫菊酯类杀虫剂（三种 I 型化合物：氯菊酯、甲醚菊酯和溴氰菊酯，以及三种 II 型化合物：氯氰菊酯、顺式氯氰菊酯和高效氯氟氰菊酯）的发育毒性，并确定斑马鱼胚胎是否可以作为研究拟除虫菊酯类发育神经毒性的合适模型。暴露于拟除虫菊酯类杀虫剂的斑马鱼胚胎死亡率和心包水肿呈剂量依赖性增加，II 型化合物的作用最强。在接近 LC50 的剂量下，氯菊酯和氯氰菊酯引起颅面畸形。这些发现与哺乳动物研究一致，表明拟除虫菊酯类在非常高的剂量下具有轻度致畸性。然而，在较低剂量下，观察到身体轴弯曲和痉挛，这与经典的拟除虫菊酯类毒性综合征相似。地西泮治疗可改善痉挛，钠离子通道拮抗剂 MS-222 治疗可改善痉挛和身体弯曲，这表明拟除虫菊酯类引起的神经毒性在斑马鱼和哺乳动物中相似。综合来看，这些数据表明，斑马鱼可能是研究拟除虫菊酯类杀虫剂发育神经毒性机制的合适替代模型，并有助于鉴定应在哺乳动物系统中进一步测试的化合物。
