dc.contributorFederal University of Ceara
dc.contributorUniversidade Estadual Paulista (UNESP)
dc.date.accessioned2022-04-29T08:33:17Z
dc.date.accessioned2022-12-20T02:53:02Z
dc.date.available2022-04-29T08:33:17Z
dc.date.available2022-12-20T02:53:02Z
dc.date.created2022-04-29T08:33:17Z
dc.date.issued2021-10-30
dc.identifierToxicon, v. 202, p. 46-52.
dc.identifier1879-3150
dc.identifier0041-0101
dc.identifierhttp://hdl.handle.net/11449/229577
dc.identifier10.1016/j.toxicon.2021.08.024
dc.identifier2-s2.0-85115635243
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/5409711
dc.description.abstractAcute 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.
dc.languageeng
dc.relationToxicon
dc.sourceScopus
dc.subjectAcute kidney injury
dc.subjectKidney perfusion
dc.subjectSildenafil
dc.subjectSnake venom
dc.titlePhosphodiesterase-5 inhibitor sildenafil attenuates kidney injury induced by Bothrops alternatus snake venom
dc.typeArtículos de revistas


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