Effects of cilostazol, a Phosphodiesterase-3 inhibitor, on kidney function and redox imbalance in acute kidney injury caused by Bothrops alternatus venom

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dc.contributor.authorMarinho, Aline Diogo
dc.contributor.authorCoelho Jorge, Antônio Rafael
dc.contributor.authorNogueira Junior, Francisco Assis
dc.contributor.authorAlison de Moraes Silveira, João
dc.contributor.authorRocha, Danilo Galvão
dc.contributor.authorNegreiros Nunes Alves, Ana Paula
dc.contributor.authorFerreira, Rui Seabra [UNESP]
dc.contributor.authorBezerra Jorge, Roberta Jeane
dc.contributor.authorAzul Monteiro, Helena Serra
dc.contributor.institutionFederal University of Ceara
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.date.accessioned2023-07-29T13:25:58Z
dc.date.available2023-07-29T13:25:58Z
dc.date.issued2022-12-01
dc.description.abstractThe mechanisms of pathogenesis of acute kidney injury (AKI) in snakebites is multifactorial and involves hemodynamic disturbances, with release of free radical causing cytotoxic effects. The phosphodiesterase-3 (PDE3) inhibitor, Cilostazol, has been reported to provide protection against renal oxidative stress. Objective: We evaluated the protective effects of cilostazol against Bothrops alternatus snake venom (BaV)-induced nephrotoxicity. Methods: Wistar rat kidneys (n = 6, 260–300 g) were isolated and perfused with Krebs-Henseleit solution containing 6 g/100 mL of bovine serum albumin. After 30 min, the kidneys were perfused with BaV to a final concentration of 1 and 3 μg/mL, and subsequently evaluated for perfusion pressure (PP), renal vascular resistance (RVR), urinary flow (UF), glomerular filtration rate (GFR), and percentage of electrolyte tubular sodium and chloride transport (%TNa+, %TCl–). Oxidative stress and renal histological analyses were performed. Results: BaV caused a reduction in all the evaluated renal parameters (PP, RVR, GFR, UF, %TNa+, and %TCl–). Although only the effects on PP and UF were reversed with cilostazol treatment, the decrease in the malondialdehyde levels, without changes in glutathione levels, further reduced the venom-induced renal tissue changes. Conclusion: Our data suggest that PDE3 is involved in BaV-induced nephrotoxicity, as cilostazol administration significantly ameliorated these effects.en
dc.description.affiliationDepartment of Physiology and Pharmacology School of Medicine Federal University of Ceara, Coronel Nunes de Melo St., 1127, CE
dc.description.affiliationDrug Research and Development Center (NPDM) Federal University of Ceara, Coronel Nunes de Melo St., 1000, CE
dc.description.affiliationDepartment of Dental Clinic School of Pharmacy Dentistry and Nursing Federal University of Ceara, Fortaleza, Monsenhor Furtado St.
dc.description.affiliationCenter for the Study of Venoms and Venomous Animals Fazenda Experimental Lageado São Paulo State University, José Barbosa de Barros St., 1780, SP
dc.description.affiliationUnespCenter for the Study of Venoms and Venomous Animals Fazenda Experimental Lageado São Paulo State University, José Barbosa de Barros St., 1780, SP
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.identifierhttp://dx.doi.org/10.1016/j.toxicon.2022.09.008
dc.identifier.citationToxicon, v. 220.
dc.identifier.doi10.1016/j.toxicon.2022.09.008
dc.identifier.issn1879-3150
dc.identifier.issn0041-0101
dc.identifier.scopus2-s2.0-85140492323
dc.identifier.urihttp://hdl.handle.net/11449/247790
dc.language.isoeng
dc.relation.ispartofToxicon
dc.sourceScopus
dc.subjectBothrops alternatus
dc.subjectKidney injury
dc.subjectKidney perfusion
dc.subjectPhosphodiesterase-3 inhibitor
dc.subjectSnake envenomation
dc.titleEffects of cilostazol, a Phosphodiesterase-3 inhibitor, on kidney function and redox imbalance in acute kidney injury caused by Bothrops alternatus venomen
dc.typeArtigo
unesp.author.orcid0000-0003-4027-0390 0000-0003-4027-0390[1]

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Botucatu - CEVAP - Centro de Estudos de Venenos e Animais Peçonhentos