Waterborne gemfibrozil challenges the hepatic antioxidant defense system and down-regulates peroxisome proliferator-activated receptor beta (PPARbeta) mRNA levels in male goldfish (Carassius auratus).
The lipid regulator gemfibrozil (GEM) is one of many human pharmaceuticals found in the aquatic environment. We previously demonstrated that GEM bioconcentrates in blood and reduces plasma testosterone levels in goldfish (Carassius auratus). In this study, we address the potential of an environmentally relevant waterborne concentration of GEM (1.5 microg/l) to induce oxidative stress in goldfish liver and whether this may be linked to GEM acting as a peroxisome proliferator (PP). We also investigate the autoregulation of the peroxisome proliferator-activated receptors (PPARs) as a potential index of exposure. The three PPAR subtypes (alpha, beta, and gamma) were amplified from goldfish liver cDNA. Goldfish exposed to a concentration higher (1500 microg/l) than environmentally relevant for 14 and 28 days significantly reduce hepatic PPARbeta mRNA levels (p<0.001). Levels of CYP1A1 mRNA were unchanged. GEM exposure significantly induced the antioxidant defense enzymes catalase (p<0.001), glutathione peroxidase (p<0.001) and glutathione-S-transferase (p=0.006) but not acyl-CoA oxidase or glutathione reductase. As GEM exposure failed to increase levels of thiobarbituric reactive substances (TBARS), we conclude that a sub-chronic exposure to GEM upregulates the antioxidant defense status of the goldfish as an adaptive response to this human pharmaceutical.
Mimeault
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C
Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, 20 Marie-Curie, Ottawa, Ontario, Canada K1N 6N5.
Trudeau
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VL
Moon
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TW
D000199:Actins / Q000096:biosynthesis / Q000378:metabolism; D042962:Acyl-CoA Oxidase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D015248:Gemfibrozil / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D006054:Goldfish / Q000378:metabolism*; D000960:Hypolipidemic Agents / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D018384:Oxidative Stress / Q000187:drug effects; D048068:PPAR-beta / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014018:Tissue Distribution; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D000199:Actins; D000975:Antioxidants; D000960:Hypolipidemic Agents; D048068:PPAR-beta; D012333:RNA, Messenger; D017392:Thiobarbituric Acid Reactive Substances; D014874:Water Pollutants, Chemical; D019363:Cytochrome P-450 CYP1A1; D042962:Acyl-CoA Oxidase; D005978:Glutathione; D015248:Gemfibrozil