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

Made available in DSpace on 2022-04-29T08:33:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-10-30 Acute 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. Department of Physiology and Pharmacology School of Medicine Federal University of Ceara, Coronel Nunes de Melo St., 1127 Drug Research and Development Center (NPDM) Federal University of Ceara, Coronel Nunes de Melo St., 1000 Department of Dental Clinic School of Pharmacy Dentistry and Nursing Federal University of Ceara, Monsenhor Furtado St. Center for the Study of Venoms and Venomous Animals Fazenda Experimental Lageado São Paulo State University, José Barbosa de Barros St. 1780 Center for the Study of Venoms and Venomous Animals Fazenda Experimental Lageado São Paulo State University, José Barbosa de Barros St. 1780