Acute and chronic effects of environmental realistic concentrations of simvastatin in danio rerio: evidences of oxidative alterations and endocrine disruptive activity

Detalhes bibliográficos
Autor(a) principal: Rebelo, D.
Data de Publicação: 2021
Outros Autores: Correia, A. T., Nunes, B.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10773/34732
Resumo: Due to their wide use, pharmaceuticals can be discarded, metabolized and excreted into the environment, potentially affecting aquatic organisms. Lipid-regulating drugs are among the most prescribed medications around the world, to control human cholesterol levels, in more than 20 million patients. Despite this massive use of lipid-regulating drugs, particularly simvastatin, the role of these drugs is not fully characterized and understood in terms of its potential toxicological effects at the environmental level. This work intended to characterize the toxicity of an acute (120 h post-fertilization) and chronic (60 days) exposure to the antihyperlipidemic drug simvastatin (in concentrations of 92.45, 184.9, 369.8, 739.6 and 1479.2 ng L-1), in the freshwater species zebrafish (Danio rerio). The concentrations hereby mentioned were implemented in both exposures, and were based on levels found in wastewater treatment plant influents (11.7 ± 3.2 μg L-1), effluents (2.65 ± 0.8 μg L-1) and Apies River (1.585 ± 0.3 μg L-1), located in Pretoria, South Africa and, particularly in the maximum levels found in effluents from wastewater treatment plants in Portugal (369.8 ng L-1). The acute effects were analysed focusing on behavioural endpoints (erratic and purposeful swimming), total distance travelled and swimming time), biomarkers of oxidative stress (the activities of the enzymes superoxide dismutase, catalase, glutathione peroxidase), biotransformation (the activity of glutathione S-transferases) and lipid peroxidation (levels of thiobarbituric acid reactive substances). Animals chronically exposed were also histologically analysed for sex determination and gonadal developmental stages identification. In terms of acute exposure, significant alterations were reported in terms of behavioural alterations (hyperactivity), followed by a general reduction in all tested biomarkers. Also, the analysis of chronically exposed fish evidenced no alterations in sex ratio and maturation stages. In addition, the analysis of chronically exposed fish evidenced no alterations in terms of sexual characteristics, suggesting that the chronic exposure of Danio rerio to simvastatin does not alter the sex ratio and maturation stages of individuals. This assumption suggests that simvastatin did not act as an endocrine disruptor. Moreover, the metabolism, neuronal interactions and the antioxidant properties of SIM seem to have modulated the hereby-mentioned results of toxicity. Results from this assay allow inferring that simvastatin can have an ecologically relevant impact in living organisms.
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spelling Acute and chronic effects of environmental realistic concentrations of simvastatin in danio rerio: evidences of oxidative alterations and endocrine disruptive activityAntihyperlipidemicBehaviourBiomarkersHistologyReproductive disruptorsZebrafishDue to their wide use, pharmaceuticals can be discarded, metabolized and excreted into the environment, potentially affecting aquatic organisms. Lipid-regulating drugs are among the most prescribed medications around the world, to control human cholesterol levels, in more than 20 million patients. Despite this massive use of lipid-regulating drugs, particularly simvastatin, the role of these drugs is not fully characterized and understood in terms of its potential toxicological effects at the environmental level. This work intended to characterize the toxicity of an acute (120 h post-fertilization) and chronic (60 days) exposure to the antihyperlipidemic drug simvastatin (in concentrations of 92.45, 184.9, 369.8, 739.6 and 1479.2 ng L-1), in the freshwater species zebrafish (Danio rerio). The concentrations hereby mentioned were implemented in both exposures, and were based on levels found in wastewater treatment plant influents (11.7 ± 3.2 μg L-1), effluents (2.65 ± 0.8 μg L-1) and Apies River (1.585 ± 0.3 μg L-1), located in Pretoria, South Africa and, particularly in the maximum levels found in effluents from wastewater treatment plants in Portugal (369.8 ng L-1). The acute effects were analysed focusing on behavioural endpoints (erratic and purposeful swimming), total distance travelled and swimming time), biomarkers of oxidative stress (the activities of the enzymes superoxide dismutase, catalase, glutathione peroxidase), biotransformation (the activity of glutathione S-transferases) and lipid peroxidation (levels of thiobarbituric acid reactive substances). Animals chronically exposed were also histologically analysed for sex determination and gonadal developmental stages identification. In terms of acute exposure, significant alterations were reported in terms of behavioural alterations (hyperactivity), followed by a general reduction in all tested biomarkers. Also, the analysis of chronically exposed fish evidenced no alterations in sex ratio and maturation stages. In addition, the analysis of chronically exposed fish evidenced no alterations in terms of sexual characteristics, suggesting that the chronic exposure of Danio rerio to simvastatin does not alter the sex ratio and maturation stages of individuals. This assumption suggests that simvastatin did not act as an endocrine disruptor. Moreover, the metabolism, neuronal interactions and the antioxidant properties of SIM seem to have modulated the hereby-mentioned results of toxicity. Results from this assay allow inferring that simvastatin can have an ecologically relevant impact in living organisms.Elsevier2022-09-22T09:41:07Z2021-01-01T00:00:00Z2021-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10773/34732eng1382-668910.1016/j.etap.2020.103522Rebelo, D.Correia, A. T.Nunes, B.info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-22T12:06:06Zoai:ria.ua.pt:10773/34732Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:05:36.860925Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Acute and chronic effects of environmental realistic concentrations of simvastatin in danio rerio: evidences of oxidative alterations and endocrine disruptive activity
title Acute and chronic effects of environmental realistic concentrations of simvastatin in danio rerio: evidences of oxidative alterations and endocrine disruptive activity
spellingShingle Acute and chronic effects of environmental realistic concentrations of simvastatin in danio rerio: evidences of oxidative alterations and endocrine disruptive activity
Rebelo, D.
Antihyperlipidemic
Behaviour
Biomarkers
Histology
Reproductive disruptors
Zebrafish
title_short Acute and chronic effects of environmental realistic concentrations of simvastatin in danio rerio: evidences of oxidative alterations and endocrine disruptive activity
title_full Acute and chronic effects of environmental realistic concentrations of simvastatin in danio rerio: evidences of oxidative alterations and endocrine disruptive activity
title_fullStr Acute and chronic effects of environmental realistic concentrations of simvastatin in danio rerio: evidences of oxidative alterations and endocrine disruptive activity
title_full_unstemmed Acute and chronic effects of environmental realistic concentrations of simvastatin in danio rerio: evidences of oxidative alterations and endocrine disruptive activity
title_sort Acute and chronic effects of environmental realistic concentrations of simvastatin in danio rerio: evidences of oxidative alterations and endocrine disruptive activity
author Rebelo, D.
author_facet Rebelo, D.
Correia, A. T.
Nunes, B.
author_role author
author2 Correia, A. T.
Nunes, B.
author2_role author
author
dc.contributor.author.fl_str_mv Rebelo, D.
Correia, A. T.
Nunes, B.
dc.subject.por.fl_str_mv Antihyperlipidemic
Behaviour
Biomarkers
Histology
Reproductive disruptors
Zebrafish
topic Antihyperlipidemic
Behaviour
Biomarkers
Histology
Reproductive disruptors
Zebrafish
description Due to their wide use, pharmaceuticals can be discarded, metabolized and excreted into the environment, potentially affecting aquatic organisms. Lipid-regulating drugs are among the most prescribed medications around the world, to control human cholesterol levels, in more than 20 million patients. Despite this massive use of lipid-regulating drugs, particularly simvastatin, the role of these drugs is not fully characterized and understood in terms of its potential toxicological effects at the environmental level. This work intended to characterize the toxicity of an acute (120 h post-fertilization) and chronic (60 days) exposure to the antihyperlipidemic drug simvastatin (in concentrations of 92.45, 184.9, 369.8, 739.6 and 1479.2 ng L-1), in the freshwater species zebrafish (Danio rerio). The concentrations hereby mentioned were implemented in both exposures, and were based on levels found in wastewater treatment plant influents (11.7 ± 3.2 μg L-1), effluents (2.65 ± 0.8 μg L-1) and Apies River (1.585 ± 0.3 μg L-1), located in Pretoria, South Africa and, particularly in the maximum levels found in effluents from wastewater treatment plants in Portugal (369.8 ng L-1). The acute effects were analysed focusing on behavioural endpoints (erratic and purposeful swimming), total distance travelled and swimming time), biomarkers of oxidative stress (the activities of the enzymes superoxide dismutase, catalase, glutathione peroxidase), biotransformation (the activity of glutathione S-transferases) and lipid peroxidation (levels of thiobarbituric acid reactive substances). Animals chronically exposed were also histologically analysed for sex determination and gonadal developmental stages identification. In terms of acute exposure, significant alterations were reported in terms of behavioural alterations (hyperactivity), followed by a general reduction in all tested biomarkers. Also, the analysis of chronically exposed fish evidenced no alterations in sex ratio and maturation stages. In addition, the analysis of chronically exposed fish evidenced no alterations in terms of sexual characteristics, suggesting that the chronic exposure of Danio rerio to simvastatin does not alter the sex ratio and maturation stages of individuals. This assumption suggests that simvastatin did not act as an endocrine disruptor. Moreover, the metabolism, neuronal interactions and the antioxidant properties of SIM seem to have modulated the hereby-mentioned results of toxicity. Results from this assay allow inferring that simvastatin can have an ecologically relevant impact in living organisms.
publishDate 2021
dc.date.none.fl_str_mv 2021-01-01T00:00:00Z
2021-01
2022-09-22T09:41:07Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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url http://hdl.handle.net/10773/34732
dc.language.iso.fl_str_mv eng
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10.1016/j.etap.2020.103522
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dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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