Abstract
BackgroundAcute 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 FindingsHematocrit, 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/SignificanceData 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.
Highlights
Envenoming resulting from snake bite is recognized nowadays as one of the major neglected public health issue within poor communities living in the rural areas of several countries throughout the world
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
Hyperuricemia has been observed in human accidents with C. d. terrificus [8] and others species of snakes [9], this parameter has not received any special attention as a relevant factor in the etiology of acute renal failure (ARF), mainly because according to the recommendation of AKIN (Acute Kidney Injury Network) the prominent criteria to identify ARF should be the detection of changes in absolute values of serum creatinine, plasma urea and urinary volume [5,10,11,12]
Summary
Envenoming resulting from snake bite is recognized nowadays as one of the major neglected public health issue within poor communities living in the rural areas of several countries throughout the world. In Brazil, bites by snakes of genus Crotalus were responsible for 7.7% of these, but accidents involving this genus originate the highest mortality (about 2%) among registered snake bites [2]. Among the species of this genus, Crotalus durissus terrificus is the most frequently implicated in these accidents [3]. Because it is well vascularized, the kidney is a vulnerable organ to venom toxicity [4]. The most serious complication of Crotalus snake bite is acute renal failure (ARF) [5]. 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
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