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Renal toxicity of Bothrops moojeni snake venom and its main myotoxins

机译:Bothrops moojeni蛇毒的肾脏毒性及其主要肌毒素

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Acute renal failure is one the most common systemic complications after snakebite, however, its pathogenesis remains obscure. In this study we evaluated the renal effects of Bothrops moojeni venom and its myotoxins (Bmtx-I and BmtxII) in rat isolated perfused kidneys. The myotoxins were purified by ion-exchange chromatography and reverse phase HPLC. The whole venom (10 mug/ml) and myotoxins (5 mug/ml) were added to the perfusion system 30 min after the beginning of each perfusion. The renal effects were compared to a control group perfused with modified Krebs-Henseleit solution alone. B. moojeni venom decreased the perfusion pressure (PP), renal vascular resistance (RVR), and the percent sodium, potassium and chloride tubular transport (%TNa+, %TK+, %TCl-). In contrast, the venom increased the urinary flow (UF), glomerular filtration rate (GFR), and the sodium, potassium and chloride excretion (ENa+, EK+, ECl-). The renal effects of myotoxin I was very similar to those of the whole venom, but there was an increase rather than a decrease in the PP and RVR. Myotoxin II had no effect on renal physiology, except for a transient decrease in %TK+. In conclusion, B. moojeni venom caused intense alterations in renal physiology, including a drop in vascular resistance associated with diuresis, natriuresis and kaliuresis. Bmtx-I had an opposite effect when compared to whole venom, showed in the parameters of PP and RVR. Bmtx-II had a mild effect in %TK+. The apparent inability of Bmtx-II to induce the renal effect similarly to Bmtx-I should be explained by the absence in the Bmtx-II of the C-terminal lysine rich region.
机译:急性肾衰竭是蛇咬后最常见的全身性并发症之一,但是其发病机理仍然不清楚。在这项研究中,我们评估了鼠尾草(Botrops moojeni)毒液及其肌毒素(Bmtx-I和BmtxII)对大鼠离体灌流肾脏的肾脏影响。通过离子交换色谱和反相HPLC纯化肌毒素。每次灌注开始30分钟后,将全部毒液(10杯/毫升)和肌毒素(5杯/毫升)添加到灌注系统中。将肾脏效果与仅灌注改良的Krebs-Henseleit溶液的对照组进行比较。 B. moojeni毒液降低了灌注压(PP),肾血管阻力(RVR)以及钠,钾和氯化物的肾小管转运百分比(%TNa +,%TK +,%TC1-)。相比之下,毒液会增加尿流量(UF),肾小球滤过率(GFR)以及钠,钾和氯的排泄(ENa +,EK +,EC1-)。肌毒素I的肾脏作用与整个毒液非常相似,但是PP和RVR的增加而不是减少。肌毒素II对肾生理没有影响,除了%TK +的短暂下降。总之,moojeni毒液引起肾脏生理的剧烈变化,包括与利尿,利尿和利尿有关的血管阻力下降。与全毒相比,Bmtx-1具有相反的作用,如PP和RVR的参数所示。 Bmtx-II对%TK +的影响较小。 Bmtx-II明显无法像Bmtx-I一样诱导肾功能,这可以通过在Bmtx-II中缺少C端赖氨酸富集区域来解释。

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