Snakebites have been recognized as a neglected public health problem in several tropical and subtropical countries. Bothrops snakebites frequently complicate with acute kidney injury (AKI) with relevant morbidity and mortality. To date, the only treatment available for Bothrops envenomation is the intravenous administration of antivenom despite its several limitations. Therefore, the study of novel therapies in Bothrops envenomation is compelling. The aim of this study was to evaluate the protective effect of Allopurinol (Allo) in an experimental model of Bothrops jararaca venom (BJ)-associated AKI. Five groups of Wistar rats were studied: Sham, Allo, BJ, BJ+Allo, BJ+ipAllo. BJ (0.25 mg/kg) was intravenously injected during 40’. Saline at same dose and infusion rate was administered to Sham and Allo groups. Allo and BJ+Allo groups received Allo (300 mg/L) in the drinking water 7 days prior to Saline or BJ infusion respectively. BJ+ipAllo rats received intraperitoneal Allo (25 mg/Kg) 40’ after BJ infusion. BJ rats showed markedly reduced glomerular filtration rate (GFR, inulin clearance) associated with intense renal vasoconstriction, hemolysis, hemoglobinuria, reduced glutathione and increased systemic and renal markers of nitro-oxidative stress (Nitrotyrosine). Allo ameliorated GFR, renal blood flow (RBF), renal vascular resistance and arterial lactate levels. In addition, Allo was associated with increased serum glutathione as well as reduced levels of plasma and renal Nitrotyrosine. Our data show that Allo attenuated BJ-associated AKI, reduced oxidative stress, improved renal hemodynamics and organ perfusion. It might represent a novel adjuvant approach for Bothrops envenomation, a new use for an old and widely available drug.

在一些热带和亚热带国家，蛇咬被公认为是被忽视的公共卫生问题。蛇行蛇咬伤常常使急性肾损伤（AKI）复杂化，并具有相关的发病率和死亡率。迄今为止，尽管两种方法都有局限性，但可用于Bothrops毒化的唯一治疗方法是静脉注射抗蛇毒血清。因此，对Bothrops毒化中的新疗法的研究令人信服。这项研究的目的是评估别嘌呤醇（Allo）在Bothrops jararaca实验模型中的保护作用。毒液（BJ）相关的AKI。研究了五组Wistar大鼠：Sham，Allo，BJ，BJ + Allo，BJ + ipAllo。在40分钟内静脉注射BJ（0.25 mg / kg）。将假手术组和同种异体组以相同剂量和输注速度输注盐水。Allo和BJ + Allo组分别在输注盐水或BJ之前7天在饮用水中接受Allo（300 mg / L）。BJ + ipAllo大鼠在BJ输注后40'接受腹膜内Allo（25 mg / Kg）。BJ大鼠显示肾小球滤过率（GFR，菊粉清除率）显着降低，与强烈的肾血管收缩，溶血，血红蛋白尿，谷胱甘肽减少以及硝基氧化应激（硝基酪氨酸）的全身和肾脏标志物升高有关。同种异体可改善GFR，肾血流量（RBF），肾血管阻力和动脉血乳酸水平。此外，Allo与血清谷胱甘肽增加以及血浆和肾硝基酪氨酸水平降低有关。我们的数据表明，同种异体可减轻BJ相关的AKI，降低氧化应激，改善肾脏血液动力学和器官灌注。它可能代表了一种新颖的辅助方法Bothrops毒化是一种古老且广泛使用的药物的新用途。