Laboratory of Pharmacology, Instituto Butantan, São Paulo, São Paulo, Brazil.
PLoS Negl Trop Dis. 2011 Sep;5(9):e1312. doi: 10.1371/journal.pntd.0001312. Epub 2011 Sep 6.
Acute renal failure is one of the most serious complications of envenoming resulting from Crotalus durissus terrificus bites. This study evaluated the relevance of hyperuricemia and oxidative stress and the effects of allopurinol and probenecid in renal dysfunction caused by direct nephrotoxicity of C. d. terrificus venom.
METHODOLOGY/PRINCIPAL FINDINGS: Hematocrit, protein, renal function and redox status were assessed in mice. High ratio of oxidized/reduced glutathione and hyperuricemia induced by C. d. terrificus venom were ameliorated by both, allopurinol or probenecid, but only allopurinol significantly reduced the lethality caused by C. d. terrificus venom. The effectiveness of probenecid is compromised probably because it promoted hypercreatinemia and hypocreatinuria and worsed the urinary hypo-osmolality in envenomed mice. In turn, the highest effectiveness of allopurinol might be due to its ability to diminish the intracellular formation of uric acid.
CONCLUSIONS/SIGNIFICANCE: Data provide consistent evidences linking uric acid with the acute renal failure induced by C. d. terrificus venom, as well as that this envenoming in mice constitutes an attractive animal model suitable for studying the hyperuricemia and that the allopurinol deserves to be clinically evaluated as an approach complementary to anti-snake venom serotherapy.
急性肾衰竭是响尾蛇属响尾蛇咬伤中毒最严重的并发症之一。本研究评估了高尿酸血症和氧化应激的相关性，以及别嘌醇和丙磺舒在响尾蛇属响尾蛇蛇毒直接肾毒性引起的肾功能障碍中的作用。
方法/主要发现：评估了小鼠的红细胞压积、蛋白质、肾功能和氧化还原状态。响尾蛇属响尾蛇蛇毒引起的氧化型/还原型谷胱甘肽比值升高和高尿酸血症，均被别嘌醇或丙磺舒改善，但只有别嘌醇能显著降低响尾蛇属响尾蛇蛇毒的致死率。丙磺舒的疗效可能受到影响，因为它会导致高肌酸血症和低肌酸尿症，并加重中毒小鼠的尿低渗性。相反，别嘌醇的最高疗效可能归因于其减少尿酸在细胞内形成的能力。
结论/意义：数据提供了一致的证据，将尿酸与响尾蛇属响尾蛇蛇毒引起的急性肾衰竭联系起来，并且该蛇毒在小鼠中的作用构成了一个有吸引力的动物模型，适合研究高尿酸血症，别嘌醇值得作为抗蛇毒血清治疗的补充方法进行临床评估。
