Environmental impacts of COVID-19 treatment: Toxicological evaluation of azithromycin and hydroxychloroquine in adult zebrafish

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dc.contributor.authorMendonça-Gomes, Juliana Moreira
dc.contributor.authorda Costa Araújo, Amanda Pereira
dc.contributor.authorda Luz, Thiarlen Marinho
dc.contributor.authorCharlie-Silva, Ives
dc.contributor.authorBraz, Helyson Lucas Bezerra
dc.contributor.authorJorge, Roberta Jeane Bezerra
dc.contributor.authorAhmed, Mohamed Ahmed Ibrahim
dc.contributor.authorNóbrega, Rafael Henrique [UNESP]
dc.contributor.authorVogel, Christoph F.A.
dc.contributor.authorMalafaia, Guilherme
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionInstituto Federal Goiano
dc.contributor.institutionUniversidade Federal de Goiás (UFG)
dc.contributor.institutionFederal University of Ceará
dc.contributor.institutionAssiut University
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionUniversity of California
dc.contributor.institutionUniversidade Federal de Uberlândia (UFU)
dc.date.accessioned2022-04-29T08:45:31Z
dc.date.available2022-04-29T08:45:31Z
dc.date.issued2021-10-10
dc.description.abstractOne of the most impact issues in recent years refers to the COVID-19 pandemic, the consequences of which thousands of deaths recorded worldwide, are still inferior understood. Its impacts on the environment and aquatic biota constitute a fertile field of investigation. Thus, to predict the impact of the indiscriminate use of azithromycin (AZT) and hydroxychloroquine (HCQ) in this pandemic context, we aim to assess their toxicological risks when isolated or in combination, using zebrafish (Danio rerio) as a model system. In summary, we observed that 72 h of exposure to AZT and HCQ (alone or in binary combination, both at 2.5 μg/L) induced the reduction of total protein levels, accompanied by increased levels of thiobarbituric acid reactive substances, hydrogen peroxide, reactive oxygen species and nitrite, suggesting a REDOX imbalance and possible oxidative stress. Molecular docking analysis further supported this data by demonstrating a strong affinity of AZT and HCQ with their potential antioxidant targets (catalase and superoxide dismutase). In the protein-protein interaction network analysis, AZT showed a putative interaction with different cytochrome P450 molecules, while HCQ demonstrated interaction with caspase-3. The functional enrichment analysis also demonstrated diverse biological processes and molecular mechanisms related to the maintenance of REDOX homeostasis. Moreover, we also demonstrated an increase in the AChE activity followed by a reduction in the neuromasts of the head when zebrafish were exposed to the mixture AZT + HCQ. These data suggest a neurotoxic effect of the drugs. Altogether, our study demonstrated that short exposure to AZT, HCQ or their mixture induced physiological alterations in adult zebrafish. These effects can compromise the health of these animals, suggesting that the increase of AZT and HCQ due to COVID-19 pandemic can negatively impact freshwater ecosystems.en
dc.description.affiliationDepartamento de Imunologia Instituto de Ciências Biomédicas Universidade de São Paulo
dc.description.affiliationLaboratório de Pesquisas Biológicas Instituto Federal Goiano
dc.description.affiliationPrograma de Pós-Graduação em Ciências Ambientais Universidade Federal de Goiás
dc.description.affiliationDepartamento de Farmacologia Instituto de Ciências Biomédicas Universidade de São Paulo
dc.description.affiliationDrug Research and Development Center Federal University of Ceará
dc.description.affiliationDepartment of Physiology and Pharmacology School of Medicine Federal University of Ceará
dc.description.affiliationPlant Protection Department Faculty of Agriculture Assiut University
dc.description.affiliationReproductive and Molecular Biology Group Department of Structural and Functional Biology Institute of Biosciences São Paulo State University
dc.description.affiliationDepartment of Environmental Toxicology and Center for Health and the Environment University of California
dc.description.affiliationPrograma de Pós-Graduação em Biotecnologia e Biodiversidade Universidade Federal de Goiás
dc.description.affiliationPrograma de Pós-Graduação em Ecologia e Conservação de Recursos Naturais Universidade Federal de Uberlândia
dc.description.affiliationPrograma de Pós-Graduação em Conservação de Recursos Naturais do Cerrado Instituto Federal Goiano
dc.description.affiliationUnespReproductive and Molecular Biology Group Department of Structural and Functional Biology Institute of Biosciences São Paulo State University
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIdCNPq: 305639/2019-6
dc.description.sponsorshipIdCNPq: 426531/2018-3
dc.identifierhttp://dx.doi.org/10.1016/j.scitotenv.2021.148129
dc.identifier.citationScience of the Total Environment, v. 790.
dc.identifier.doi10.1016/j.scitotenv.2021.148129
dc.identifier.issn1879-1026
dc.identifier.issn0048-9697
dc.identifier.scopus2-s2.0-85108075667
dc.identifier.urihttp://hdl.handle.net/11449/231459
dc.language.isoeng
dc.relation.ispartofScience of the Total Environment
dc.sourceScopus
dc.subjectAntibiotic
dc.subjectAntimalarial
dc.subjectDanio rerio
dc.subjectEcotoxicity
dc.subjectSARs-Cov-2
dc.subjectWater pollution
dc.titleEnvironmental impacts of COVID-19 treatment: Toxicological evaluation of azithromycin and hydroxychloroquine in adult zebrafishen
dc.typeArtigo

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Artigos - Microbiologia e Imunologia - IBB