title: Inhibition of immune responses and related proteins in Rhamdia quelen exposed to diclofenac.
abstract: Nonsteroidal anti-inflammatory drugs are among the most widely detected pharmaceuticals in surface water worldwide. The nonsteroidal anti-inflammatory drug diclofenac is used to treat many types of pain and inflammation. Diclofenac's potential to cause adverse effects in exposed wildlife is a growing concern. To evaluate the effects of waterborne diclofenac on the immune response in Rhamdia quelen (South American catfish), fish were exposed to 3 concentrations of diclofenac (0.2, 2.0, and 20.0 μg/L) for 14 d. Some of the exposed fish were also given an intraperitoneal injection on day 14 of 1 mg/kg of carrageenan to evaluate cell migration to the peritoneum. Total blood leukocyte count and carrageenan-induced leukocyte migration to the peritoneal cavity, particularly of polymorphonuclear cells, were significantly affected for all diclofenac exposure groups. Nitric oxide production was significantly reduced in the diclofenac-treated fish. Plasma and kidney proteins were analyzed by means of liquid chromatography-tandem mass spectrometry in a shotgun proteomic approach. In both plasma and kidney of diclofenac-exposed R. quelen, the expression of 20 proteins related to the inflammatory process, nitric oxide production, leukocyte migration, and the complement cascade was significantly altered. In addition, class I major histocompatibility complex was significantly decreased in plasma of diclofenac-treated fish. Thus, waterborne exposure to diclofenac could lead to suppression of the innate immune system in R. quelen. Environ Toxicol Chem 2017;36:2092-2107. © 2017 SETAC.
authors.affiliation: Department of Pharmacology, Federal University of Parana, Curitiba-Paraná, Brazil.|Department of Biomedicine, Positivo University, Curitiba-Paraná, Brazil.
authors.forename: João L C
authors.initials: JLC
authors.lastname: Ribas
authors.affiliation: Water Science and Technology, Aquatic Contaminants Research Division, Environment and Climate Change Canada, Burlington, Ontario, Canada.
authors.forename: James P
authors.initials: JP
authors.lastname: Sherry
authors.affiliation: Department of Pharmacology, Federal University of Parana, Curitiba-Paraná, Brazil.
authors.forename: Aleksander R
authors.initials: AR
authors.lastname: Zampronio
authors.affiliation: Department of Pharmacology, Federal University of Parana, Curitiba-Paraná, Brazil.
authors.forename: Helena C
authors.initials: HC
authors.lastname: Silva de Assis
authors.affiliation: Water Science and Technology, Aquatic Contaminants Research Division, Environment and Climate Change Canada, Burlington, Ontario, Canada.
authors.forename: Denina B D
authors.initials: DBD
authors.lastname: Simmons
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D001772:Blood Cell Count; D001798:Blood Proteins / Q000032:analysis*; D002351:Carrageenan / Q000494:pharmacology; D002397:Catfishes / Q000097:blood / Q000276:immunology*; D003165:Complement System Proteins / Q000032:analysis; D004008:Diclofenac / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000097:blood; D007108:Immune Tolerance / Q000187:drug effects*; D007111:Immunity, Cellular / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D040901:Proteomics; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001798:Blood Proteins; D015395:Histocompatibility Antigens Class I; D014874:Water Pollutants, Chemical; D004008:Diclofenac; D009569:Nitric Oxide; D002351:Carrageenan; D003165:Complement System Proteins
keywords: Cell migration; Complement system; Hematology; Nitric oxide production; Proteomics