title: Non-steroidal anti-inflammatory drugs disrupt the heat shock response in rainbow trout.
abstract: Non-steroidal anti-inflammatory drugs (NSAIDS) have been detected in the aquatic environment, but little is known about either their impact or mode of action in aquatic organisms. We tested the hypothesis that NSAIDs disrupt the evolutionarily conserved heat shock response, critical for defense against stressor-mediated proteotoxicity, in rainbow trout (Oncorhynchus mykiss). Trout fry were exposed by immersion to a range of salicylate or ibuprofen concentrations (1, 10, 100 or 1000 microg/L) for 4d. Ibuprofen, but not salicylate, at all concentrations induced heat shock protein 70 (hsp70) in trout liver. We used the highest concentration of the drugs to investigate their mode of action on the heat shock response. Fry were subjected to a standardized heat shock, 10 degrees C above ambient (13 degrees C) for 1h, and the temporal changes in liver hsp70 mRNA and protein content as well as glucose dynamics during recovery from the heat stressor assessed. Ibuprofen exposure did not modify hsp70 mRNA abundance, but significantly depressed the heat shock-induced hsp70 protein expression in the liver and gill of trout. Salicylate exposure elevated hsp70 mRNA abundance and delayed the hsp70 expression after a heat shock. Liver glucose levels and the activities of hexokinase, pyruvate kinase and lactate dehydrogenase, were elevated by NSAIDs suggesting enhanced tissue glycolytic capacity. Effects on whole body glucose dynamics, induced by the heat shock, were either absent with ibuprofen or completely modified by salicylate. Overall, NSAIDs disrupt the heat shock response in rainbow trout, while the mode of action of salicylate and ibuprofen in impacting the cellular stress response appears distinct.
authors.affiliation: Department of Biology, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1.
authors.forename: Amélie
authors.initials: A
authors.lastname: Gravel
authors.forename: Mathilakath M
authors.initials: MM
authors.lastname: Vijayan
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity*; D004781:Environmental Exposure; D015870:Gene Expression / Q000187:drug effects; D005880:Gills / Q000187:drug effects; D005947:Glucose / Q000032:analysis; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D018869:Heat-Shock Response / Q000187:drug effects*; D006358:Hot Temperature; D007052:Ibuprofen / Q000008:administration & dosage / Q000633:toxicity*; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D017686:Oncorhynchus mykiss / Q000502:physiology*; D012459:Salicylates / Q000008:administration & dosage / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018840:HSP70 Heat-Shock Proteins; D012459:Salicylates; D014874:Water Pollutants, Chemical; D005947:Glucose; D007052:Ibuprofen