title: Effects of anti-inflammatory drugs in primary kidney cell culture of a freshwater fish.
abstract: The non-steroidal anti-inflammatory drugs are emerging contaminants in aquatic ecosystems. This study aimed to evaluate toxic effects of some representative drugs of this pharmaceutical group on primary culture of monocytic lineage of Hoplias malabaricus anterior kidney. The effects of diclofenac, acetaminophen and ibuprofen in cell viability, lipopolysaccharide (LPS)-induced NO production and genotoxicity were evaluated. Cytometry analysis CD11b(+) cells showed 71.5% of stem cells, 19.5% of macrophages and 9% of monocytes. Cell viability was lower in the ficoll compared to percoll separation. LPS-induced NO production by these cells was blocked after treatment with dexamethasone and NG-Methyl-L-Arginine (L-NMMA). Exposure of the cells to diclofenac (0.2-200 ng/mL), acetaminophen (0.025-250 ng/mL) ibuprofen (10-1000 ng/mL) reduced basal NO production and inhibited LPS-induced NO production at all concentrations after 24 h of exposure. Genotoxicity occurred at the highest concentration of diclofenac and at the intermediary concentration of acetaminophen. Genotoxicity was also observed by ibuprofen. In summary, the pharmaceuticals influenced NO production and caused DNA damage in monocytic cells suggesting that these drugs can induce immunosuppression and genotoxicity in fish.
authors.affiliation: Department of Pharmacology, Federal University of Parana, 81531-980 Curitiba-Paraná, Brazil.
authors.forename: João Luiz Coelho
authors.initials: JL
authors.lastname: Ribas
authors.affiliation: Ecology and Conservation Post-graduate Program, Federal University of Paraná, 81531-980 Curitiba-Paraná, Brazil.
authors.forename: Cesar A
authors.initials: CA
authors.lastname: da Silva
authors.affiliation: Department of Cellular Biology, Federal University of Paraná, 81531-980 Curitiba-Paraná, Brazil.
authors.forename: Lucas
authors.initials: L
authors.lastname: de Andrade
authors.affiliation: Department of Genetics, Federal University of Paraná, 81531-980 Curitiba-Paraná, Brazil.
authors.forename: Gabrieli Limberger
authors.initials: GL
authors.lastname: Galvan
authors.affiliation: Department of Genetics, Federal University of Paraná, 81531-980 Curitiba-Paraná, Brazil.
authors.forename: Marta Margarete
authors.initials: MM
authors.lastname: Cestari
authors.affiliation: Department of Cellular Biology, Federal University of Paraná, 81531-980 Curitiba-Paraná, Brazil.
authors.forename: Edvaldo S
authors.initials: ES
authors.lastname: Trindade
authors.affiliation: Department of Pharmacology, Federal University of Parana, 81531-980 Curitiba-Paraná, Brazil.
authors.forename: Aleksander R
authors.initials: AR
authors.lastname: Zampronio
authors.affiliation: Department of Pharmacology, Federal University of Parana, 81531-980 Curitiba-Paraná, Brazil. Electronic address: helassis@ufpr.br.
authors.forename: Helena C Silva
authors.initials: HC
authors.lastname: de Assis
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D060126:Characidae / Q000378:metabolism*; D004008:Diclofenac / Q000494:pharmacology; D007052:Ibuprofen / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009152:Mutagenicity Tests; D009569:Nitric Oxide / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D004008:Diclofenac; D009569:Nitric Oxide; D007052:Ibuprofen
keywords: Anti-inflammatory; Cell culture; Emerging contaminants; Genotoxicity; Immunosuppression