Phosphodiesterase-5 inhibitor sildenafil attenuates kidney injury induced by Bothrops alternatus snake venom

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Autor(es): dc.contributorFederal University of Ceara-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.creatorJorge, Antônio Rafael Coelho-
Autor(es): dc.creatorMarinho, Aline Diogo-
Autor(es): dc.creatorSilveira, João Alison de Moraes-
Autor(es): dc.creatorNogueira Junior, Francisco Assis-
Autor(es): dc.creatorde Aquino, Pedro Everson Alexandre-
Autor(es): dc.creatorAlves, Ana Paula Negreiros Nunes-
Autor(es): dc.creatorJorge, Roberta Jeane Bezerra-
Autor(es): dc.creatorFerreira Junior, Rui Seabra-
Autor(es): dc.creatorMonteiro, Helena Serra Azul-
Data de aceite: dc.date.accessioned2025-08-21T21:36:25Z-
Data de disponibilização: dc.date.available2025-08-21T21:36:25Z-
Data de envio: dc.date.issued2022-04-29-
Data de envio: dc.date.issued2022-04-29-
Data de envio: dc.date.issued2021-10-29-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1016/j.toxicon.2021.08.024-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/229577-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/229577-
Descrição: dc.descriptionAcute kidney injury pathogenesis in envenoming by snakes is multifactorial and involves immunologic reactions, hemodynamic disturbances, and direct nephrotoxicity. Sildenafil (SFC), a phosphodiesterase 5 inhibitor, has been reported to protect against pathological kidney changes. Objective: This study aimed to investigate the protective effect of sildenafil against Bothrops alternatus snake venom (BaV)-induced nephrotoxicity. Methods: Kidneys from Wistar rats (n = 6, weighing 260–300 g) were isolated and divided into four groups: (1) perfused with a modified Krebs-Henseleit solution (MKHS) containing 6 g% of bovine serum albumin; (2) administered 3 μg/mL SFC; (3) perfused with 3 μg/mL BaV; and (4) administered SFC + BaV, both at 3 μg/mL. Subsequently, the 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−, respectively) were evaluated. The cyclic guanosine monophosphate (cGMP) levels were analyzed in the perfusate, and the kidneys were removed to perform oxidative stress and histopathological analyses. Results: All renal parameters evaluated were reduced with BaV. In the SFC + BaV group, SFC restored PP to normal values and promoted a significant increase in %TNa+ and %TCl−. cGMP levels were increased in the SFC + BaV group. The oxidative stress biomarkers, malondialdehyde (MDA) and glutathione (GSH), were reduced by BaV. In the SFC + BaV group, a decrease in MDA without an increase in GSH was observed. These findings were confirmed by histological analysis, which showed improvement mainly in tubulis. Conclusion: Our data suggest the involvement of phosphodiesterase-5 and cGMP in BaV-induced nephrotoxicity since its effects were attenuated by the administration of SFC.-
Descrição: dc.descriptionDepartment of Physiology and Pharmacology School of Medicine Federal University of Ceara, Coronel Nunes de Melo St., 1127-
Descrição: dc.descriptionDrug Research and Development Center (NPDM) Federal University of Ceara, Coronel Nunes de Melo St., 1000-
Descrição: dc.descriptionDepartment of Dental Clinic School of Pharmacy Dentistry and Nursing Federal University of Ceara, Monsenhor Furtado St.-
Descrição: dc.descriptionCenter for the Study of Venoms and Venomous Animals Fazenda Experimental Lageado São Paulo State University, José Barbosa de Barros St. 1780-
Descrição: dc.descriptionCenter for the Study of Venoms and Venomous Animals Fazenda Experimental Lageado São Paulo State University, José Barbosa de Barros St. 1780-
Formato: dc.format46-52-
Idioma: dc.languageen-
Relação: dc.relationToxicon-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectAcute kidney injury-
Palavras-chave: dc.subjectKidney perfusion-
Palavras-chave: dc.subjectSildenafil-
Palavras-chave: dc.subjectSnake venom-
Título: dc.titlePhosphodiesterase-5 inhibitor sildenafil attenuates kidney injury induced by Bothrops alternatus snake venom-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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