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Effects of gemfibrozil on lipid metabolism, steroidogenesis and reproduction in the fathead minnow (Pimephales promelas)
Skolness, S., E. Durhan, K. Jensen, M. Kahl, L. Makynen, D. Villeneuve, AND G. Ankley. Effects of gemfibrozil on lipid metabolism, steroidogenesis and reproduction in the fathead minnow (Pimephales promelas). ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, 31(11):2615-2624, (2012).
The objective of the present study was to assess the potential physiological and reproductive impacts of gemfibrozil on fathead minnows (Pimephales promelas).
Fibrates are a class of pharmaceuticals that indirectly modulate cholesterol biosynthesis through effects on peroxisome proliferator-activated receptors (PPARs), which are transcriptional cofactors that regulate expression of genes related to lipid metabolism. Gemfibrozil is a fibrate that has been detected in wastewater treatment plant influent, effluents and drinking water. The objective of the present study was to assess the potential physiological and reproductive impacts of gemfibrozil on fathead minnows (Pimephales promelas). Adult fish were exposed to gemfibrozil in two different studies. The first was a short-term test with water concentrations of 0, 15 and 600 µg gemfibrozil/L, with sampling on days 2 and 8. Plasma cholesterol concentrations were significantly reduced in males exposed to 600 µg gemfibrozil/L for 8-d. In addition, expression of several hepatic genes important to lipid metabolism was altered, suggesting that gemfibrozil does affect lipid metabolism in fish. Following the short-term test, a 21-d study was conducted to further investigate effects on lipid metabolism and steroidogenesis, as well as assess potential impacts of gemfibrozil on reproduction. Adult fish were exposed to water concentrations of 0, 1.5, 15, 600 and 1500 µg gemfibrozil/L. Exposure to 1500 µg gemfibrozil/L caused a modest reduction in fecundity. However, gemfibrozil had no consistent effect on plasma cholesterol, triglycerides or sex steroids in the 21-d exposure. Further, there was no significant effect on the activity of fatty acyl-coenzyme A oxidase or expression of related genes, suggesting gemfibrozil is not a potent PPAR activator in fathead minnows. Increases in expression of hepatic cytochrome P4503a suggest that this isozyme could be involved in the metabolism of gemfibrozil in fish. Overall, although gemfibrozil caused a reduction in reproduction at high test concentration, there was no evidence for significant physiological or reproducti