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

• Autor(a) principal: Marinho, Aline Diogo
• Data de Publicação: 2022
• Outros Autores: Coelho Jorge, Antônio Rafael, Nogueira Junior, Francisco Assis, Alison de Moraes Silveira, João, Rocha, Danilo Galvão, Negreiros Nunes Alves, Ana Paula, Ferreira, Rui Seabra [UNESP], Bezerra Jorge, Roberta Jeane, Azul Monteiro, Helena Serra
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.1016/j.toxicon.2022.09.008; http://hdl.handle.net/11449/247790
• topic: Bothrops alternatus; Kidney injury; Kidney perfusion; Phosphodiesterase-3 inhibitor; Snake envenomation

The 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.