Effects of gemfibrozil on lipid metabolism, steroidogenesis, and reproduction in the fathead minnow (Pimephales promelas).
Fibrates are a class of pharmaceuticals that indirectly modulate cholesterol biosynthesis through effects on peroxisome proliferator-activated receptors. Gemfibrozil is a fibrate that has been detected in wastewater treatment plant influents, 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). 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, sampling after 2 or 8 d of exposure. 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. A 21-d study was conducted to investigate further the effects on lipid metabolism and steroidogenesis as well as to assess potential impacts of gemfibrozil on reproduction. Fish were exposed to water concentrations of 0, 1.5, 15, 600, and 1,500 µg gemfibrozil/L. Exposure to 1,500 µg gemfibrozil/L caused a modest, but not significant, reduction in fecundity. However, gemfibrozil had no consistent effect on plasma cholesterol, triglycerides, or sex steroids after 21 d of exposure. The present study showed no evidence for significant physiological or reproductive impacts of gemfibrozil at an environmentally relevant concentration of 1.5 µg/L.
Toxicology Graduate Program, University of Minnesota, Duluth, MN, USA. skoln005@umn.edu
Sarah Y
SY
Skolness
Elizabeth J
EJ
Durhan
Kathleen M
KM
Jensen
Michael D
MD
Kahl
Elizabeth A
EA
Makynen
Daniel L
DL
Villeneuve
Gerald T
GT
Ankley
D000818:Animals; D003530:Cyprinidae / Q000097:blood / Q000502:physiology*; D005260:Female; D005298:Fertility; D015248:Gemfibrozil / Q000494:pharmacology*; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D012098:Reproduction / Q000187:drug effects*; D013256:Steroids / Q000096:biosynthesis*; D023382:Toxicity Tests, Acute; D059551:Toxicity Tests, Subacute; D014874:Water Pollutants, Chemical / Q000494:pharmacology*
D013256:Steroids; D014874:Water Pollutants, Chemical; D015248:Gemfibrozil