Effects of chronic exposure to benzalkonium chloride in Oncorhynchus mykiss: cholinergic neurotoxicity, oxidative stress, peroxidative damage and genotoxicity.
Benzalkonium chloride (BAC) is one of the most used conservatives in pharmaceutical preparations. However, its use is limited to a small set of external use formulations, due to its high toxicity. Benzalkonium chloride effects are related to the potential exertion of deleterious effects, mediated via oxidative stress and through interaction with membrane enzymes, leading to cellular damage. To address the ecotoxicity of this specific compound rainbow trouts were chronically exposed to BAC at environmental relevant concentrations (ranging from 0.100 to 1.050mg/L), and the biological response of cholinergic neurotoxicity, modulation of the antioxidant defense, phase II metabolism, lipid peroxidation and genotoxicity was studied. The obtained results showed a dual pattern of antioxidant response, with significant alterations in catalase activity (starting at 0.180mg/L), and lipid peroxidation, for intermediate (0.180 and 0.324mg/L) concentrations. No significant alterations occurred for glutathione-S-transferases activity. An unexpected increased of the acetylcholinesterase activity was also recorded for the individuals exposed to higher concentrations of BAC (starting at 0.180mg/L). Furthermore, exposure to BAC resulted in the establishment of genotoxic alterations, observable (for the specific case of the comet assay results) for all tested BAC concentrations. However, and considering that the oxidative response was not devisable, other mechanisms may be involved in the genotoxic effects reported here.
Faculdade de Ciências da Universidade do Porto (FCUP), Rua do Campo Alegre s/n, 4169-007 Porto, Portugal; Centro de Estudos do Ambiente e do Mar (CESAM), Universidade de Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.
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Antunes
Centro de Estudos do Ambiente e do Mar (CESAM), Universidade de Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal; Departamento de Biologia, Campus Universitário de Santiago, Universidade de Aveiro, 3810-193 Aveiro, Portugal. Electronic address: nunes.b@ua.pt.
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Nunes
Faculdade de Ciências da Universidade do Porto (FCUP), Rua do Campo Alegre s/n, 4169-007 Porto, Portugal.
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Rodrigues
Faculdade de Ciências da Universidade do Porto (FCUP), Rua do Campo Alegre s/n, 4169-007 Porto, Portugal.
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Nunes
Faculdade de Ciências da Saúde da Universidade Fernando Pessoa (FCS/UFP), Rua Carlos da Maia 296, 4200-150, Porto, Portugal.
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Fernandes
Faculdade de Ciências da Saúde da Universidade Fernando Pessoa (FCS/UFP), Rua Carlos da Maia 296, 4200-150, Porto, Portugal; Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR-CIMAR), Rua dos Bragas 289, 450-123 Porto, Portugal.
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Correia
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001548:Benzalkonium Compounds / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D020552:Comet Assay; D004249:DNA Damage; D005123:Eye / Q000187:drug effects / Q000201:enzymology; D029941:Fish Proteins / Q000378:metabolism; D005880:Gills / Q000187:drug effects / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000235:genetics / Q000378:metabolism; D017686:Oncorhynchus mykiss / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011310:Preservatives, Pharmaceutical / Q000633:toxicity*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D001548:Benzalkonium Compounds; D029941:Fish Proteins; D011310:Preservatives, Pharmaceutical; D017392:Thiobarbituric Acid Reactive Substances; D014874:Water Pollutants, Chemical; D008315:Malondialdehyde; D002374:Catalase; D005982:Glutathione Transferase; D000110:Acetylcholinesterase
AChE; Biomarkers; Catalase; Comet assay; Conservatives; ENAs; GSTs; Rainbow trout; TBARS