Marinho Aline Diogo, Coelho Jorge Antônio Rafael, Nogueira Junior Francisco Assis, Alison de Moraes Silveira João, Rocha Danilo Galvão, Negreiros Nunes Alves Ana Paula, Ferreira Rui Seabra, Bezerra Jorge Roberta Jeane, Azul Monteiro Helena Serra
Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceara, Coronel Nunes de Melo St., 1127, 60.430-275, Fortaleza, CE, Brazil; Drug Research and Development Center (NPDM), Federal University of Ceara, Coronel Nunes de Melo St., 1000, 60.430-275, Fortaleza, CE, Brazil.
Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceara, Coronel Nunes de Melo St., 1127, 60.430-275, Fortaleza, CE, Brazil; Drug Research and Development Center (NPDM), Federal University of Ceara, Coronel Nunes de Melo St., 1000, 60.430-275, Fortaleza, CE, Brazil.
Toxicon. 2022 Dec;220:106922. doi: 10.1016/j.toxicon.2022.09.008. Epub 2022 Sep 24.
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.
We evaluated the protective effects of cilostazol against Bothrops alternatus snake venom (BaV)-induced nephrotoxicity.
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.
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.
Our data suggest that PDE3 is involved in BaV-induced nephrotoxicity, as cilostazol administration significantly ameliorated these effects.
蛇咬伤所致急性肾损伤（AKI）的发病机制是多因素的，涉及血流动力学紊乱，自由基释放会产生细胞毒性作用。据报道，磷酸二酯酶-3（PDE3）抑制剂西洛他唑可提供肾脏氧化应激保护作用。
我们评估了西洛他唑对交替锯鳞蝰蛇毒（BaV）诱导的肾毒性的保护作用。
分离Wistar大鼠肾脏（n = 6，体重260 - 300 g），并用含6 g/100 mL牛血清白蛋白的克雷布斯-亨氏液灌注。30分钟后，用BaV灌注肾脏，使其终浓度达到1和3 μg/mL，随后评估灌注压（PP）、肾血管阻力（RVR）、尿流（UF）、肾小球滤过率（GFR）以及电解质肾小管钠和氯转运百分比（%TNa、%TCl）。进行氧化应激和肾脏组织学分析。
BaV导致所有评估的肾脏参数（PP、RVR、GFR、UF、%TNa和%TCl）降低。虽然西洛他唑治疗仅逆转了对PP和UF的影响，但丙二醛水平降低，谷胱甘肽水平无变化，进一步减轻了毒液诱导的肾脏组织变化。
我们的数据表明PDE3参与了BaV诱导的肾毒性，因为给予西洛他唑可显著改善这些影响。
