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PM17 Pharmaceuticals (PM278) Changes to Arachidonic Acid Signaling by Pharmaceuticals in Fish. Lister, A1, Van Der Kraak, G1, 1 University of Guelph, Guelph, ON, Canada ABSTRACT- Chemical analyses of sewage effluents and surface waters throughout North America have indicated the presence of several different non-steroidal anti-inflammatory drugs (NSAID). Many of these compounds act by inhibiting both isoforms of cyclooxygenase (COX-1 and COX-2); the enzymes that are responsible for the conversion of arachidonic acid (AA) to its prostanoid metabolites. These drugs are of special concern because studies have suggested that prostaglandins (PG) are involved in the regulation of development, gonadal steroidogenesis, oocyte maturation, and sexual behaviours in fish. In order to address the potential risks that environmental NSAID pose to fish development and reproduction, we have undertaken studies using zebrafish as a model species. Our results confirm that PG are involved in the regulation of ovulation in zebrafish, and preliminary studies have shown that female zebrafish exposed to indomethacin (100ug/L) for 24 hr have reduced levels of PG. In vitro studies are being conducted to complement this in vivo work and have shown that PG and sex steroid synthesis is inhibited in AA-stimulated follicles exposed to both selective and non-selective COX inhibitors. These experiments are the basis of future studies that will confirm the mechanism of PG inhibition by NSAID (COX enzyme inhibition), and the impact of NSAID on ovulation rates and embryonic development in zebrafish in a laboratory setting. Key words: reproduction, fish , pharmaceuticals, prostaglandins |
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