Laboratory of Pharmacology, Instituto Butantan, Av. Vital Brasil, 1500, 05503-900 São Paulo, SP, Brazil.
Toxicon. 2011 Jan;57(1):148-56. doi: 10.1016/j.toxicon.2010.11.006. Epub 2010 Nov 16.
Snake bite accidents by Bothrops genus is an important public health issue in Brazil and one of its most serious complications is the acute kidney injury (AKI). Here we evaluated the effects of Bothrops jararaca venom (vBj) and the treatments with lipoic acid (LA) and simvastatin (SA) on renal function, aminopeptidase (AP) activities and renal redox status. Primordial events for establishment of AKI by vBj were hyperuricemia, hypercreatinemia, urinary hyperosmolality, renal oxidative stress and reduction of hematocrit and protein content in the membrane of renal cortex and medulla and in the plasma. In the renal cortex and medulla the changes caused by vBj in soluble and membrane-bound AP activities had a similar pattern. The beneficial effects of LA and SA on envenomed mice were similar on the hyperuricemia, renal oxidative stress and reduction of hematocrit. LA mitigated the hypercreatinemia, but exacerbated the urinary urea and creatinine, whereas SA mitigated the decrease of plasma urea, urinary hyperosmolality and hypercreatinuria induced by vBj. The beneficial effects of LA and especially of SA on renal effects of vBj open a new perspective for clinical investigations of these drugs as coadjuvant agents in the serotherapy of Bothrops envenomation.
巴西的响尾蛇属蛇咬伤事故是一个重要的公共卫生问题，其最严重的并发症之一是急性肾损伤（AKI）。在这里，我们评估了矛头蝮蛇毒液（vBj）以及硫辛酸（LA）和辛伐他汀（SA）治疗对肾功能、氨基肽酶（AP）活性和肾脏氧化还原状态的影响。vBj 导致 AKI 的初始事件是高尿酸血症、高肌酸血症、尿高渗、肾氧化应激以及肾皮质和髓质及血浆中红细胞比容和蛋白质含量的降低。vBj 在可溶性和膜结合的 AP 活性中引起的变化具有相似的模式。LA 和 SA 对中毒小鼠的有益作用在高尿酸血症、肾氧化应激和红细胞比容降低方面相似。LA 减轻了高肌酸血症，但加剧了尿尿素和肌酐，而 SA 减轻了 vBj 引起的血浆尿素、尿高渗和高肌酸尿的减少。LA 和特别是 SA 对 vBj 肾脏作用的有益作用为这些药物作为响尾蛇中毒血清治疗的辅助剂的临床研究开辟了新的前景。
