Phosphodiesterase-5 inhibitor sildenafil attenuates kidney injury induced by Bothrops alternatus snake venom. (30th October 2021)

• Record Type: Journal Article
• Authors: Jorge, Antônio Rafael Coelho; Marinho, Aline Diogo; Silveira, João Alison de Moraes; Nogueira Junior, Francisco Assis; de Aquino, Pedro Everson Alexandre; Alves, Ana Paula Negreiros Nunes; Jorge, Roberta Jeane Bezerra; Ferreira Junior, Rui Seabra; Monteiro, Helena Serra Azul
• Is Part Of: Toxicon. Volume 202(2021)
• Page Start: 46
• Page End: 52
• Publication Date: 2021-10-30
• Subjects: Acute kidney injury -- Snake venom -- Kidney perfusion -- Sildenafil; AKI acute kidney injury -- BaV Bothrops alternatus snake venom -- cGMP cyclic guanosine monophosphate -- GFR glomerular filtration rate -- GSH reduced form of glutathione -- MDA malondialdehyde -- MKHS modified Krebs-Henseleit solution -- PDE phosphodiesterase -- PP perfusion pressure -- RVR renal vascular resistance -- SFC Sildenafil citrate -- UF urinary flow -- %TNa+ percentage of total tubular sodium transport -- %TCl− percentage of total tubular chloride transport; Toxins -- Periodicals; Venom -- Periodicals; 615.9
• DOI: 10.1016/j.toxicon.2021.08.024
• Languages: English
• ISSNs: 0041-0101

Abstract

Abstract: 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 ( Ba V)-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 Ba V; and (4) administered SFC + Ba V, 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 Ba V. In the SFC + Ba V group, SFC restored PP to normal values and promoted a significant increase in %TNa + and %TCl − . cGMP levels were increased in the SFC + Ba V group. The oxidative stress biomarkers, malondialdehyde (MDA) and glutathione (GSH), were reduced by Ba V. In the SFC + Ba V 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 Ba V-induced nephrotoxicity since its effects were attenuated by the administration of SFC. Highlights: Sildenafil (SFC) protects kidney against B. alternatus snake venom ( Ba V) effects. SFC reversed vascular and functional alterations induced by Ba V. SFC reduced lipid peroxidation caused by Ba V. SFC improved histological alterations induced by Ba V. SFC further enhanced Ba V-induced increase in cGMP kidney levels.