Niemuth Nicholas J, Jordan Renee, Crago Jordan, Blanksma Chad, Johnson Rodney, Klaper Rebecca D
School of Freshwater Sciences, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
Environ Toxicol Chem. 2015 Feb;34(2):291-6. doi: 10.1002/etc.2793. Epub 2014 Dec 31.
Pharmaceuticals and personal care products (PPCPs) are emerging contaminants that have been found ubiquitously in wastewater and surface waters around the world. A major source of these compounds is incomplete metabolism in humans and subsequent excretion in human waste, resulting in discharge into surface waters by wastewater treatment plant (WWTP) effluent. One pharmaceutical found in particularly high abundance in recent WWTP effluent and surface water studies is metformin, one of the world's most widely prescribed antidiabetic drugs. Interactions between insulin signaling and steroidogenesis suggest potential endocrine-disrupting effects of metformin found in the aquatic environment. Adult fathead minnows (Pimephales promelas) were chronically exposed to metformin for 4 wk, at 40 µg/L, a level similar to the average found in WWTP effluent in Milwaukee, Wisconsin, USA. Genetic endpoints related to metabolism and endocrine function as well as reproduction-related endpoints were examined. Metformin treatment induced significant up-regulation of messenger ribonucleic acid (mRNA) encoding the egg-protein vitellogenin in male fish, an indication of endocrine disruption. The present study, the first to study the effects of environmentally relevant metformin exposure in fathead minnows, demonstrates the need for further study of the endocrine-disrupting effects of metformin in aquatic organisms.
药品和个人护理产品（PPCPs）是新出现的污染物，已在世界各地的废水和地表水中普遍发现。这些化合物的一个主要来源是人体新陈代谢不完全以及随后随人类排泄物排出，导致污水处理厂（WWTP）废水排放到地表水中。在最近的污水处理厂废水和地表水研究中发现含量特别高的一种药物是二甲双胍，它是世界上处方最广泛的抗糖尿病药物之一。胰岛素信号传导和类固醇生成之间的相互作用表明，在水生环境中发现的二甲双胍可能具有内分泌干扰作用。成年黑头呆鱼（Pimephales promelas）在40μg/L的浓度下长期暴露于二甲双胍4周，该浓度与美国威斯康星州密尔沃基市污水处理厂废水中的平均浓度相似。研究了与代谢和内分泌功能相关的基因终点以及与繁殖相关的终点。二甲双胍处理导致雄性鱼类中编码卵蛋白卵黄蛋白原的信使核糖核酸（mRNA）显著上调，这表明存在内分泌干扰。本研究首次研究了环境相关浓度的二甲双胍对黑头呆鱼的影响，表明有必要进一步研究二甲双胍对水生生物的内分泌干扰作用。
