Effects of cilostazol, a Phosphodiesterase-3 inhibitor, on kidney function and redox imbalance in acute kidney injury caused by Bothrops alternatus venom
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2022-12-01
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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.
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Bothrops alternatus, Kidney injury, Kidney perfusion, Phosphodiesterase-3 inhibitor, Snake envenomation
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Toxicon, v. 220.