Martins Alice M C, Sousa Fabiola C M, Barbosa Paulo S F, Toyama Marcos H, Toyama Daniela O, Aprígio Cleidiana C, Queiroz Maria G R, Guarnieri Mirian C, Havt Alexandre, de Menezes Dalgimar B, Fonteles Manassés C, Monteiro Helena S A
Department of Clinical and Toxicological Analysis, Federal University of Ceara, Fortaleza, Ceara, Brazil.
Toxicon. 2005 Nov;46(6):595-9. doi: 10.1016/j.toxicon.2005.06.004. Epub 2005 Sep 15.
Acute renal failure is the most common complication in the lethal cases caused by snakebites in Brazil. Among the Brazilian venom snakes, Bothrops erythromelas is responsible for the majority of accidents in Northeastern Brazil. Didelphis marsupialis serum could inhibit myonecrotic, hemorrhagic, edematogenic hyperalgesic and lethal effects of envenomation determined by ophidian bites. In the present study, we evaluated the action of the anti-bothropic factor isolated from D. marsupialis on the renal effects promoted by B. erythromelas venom without systemic interference. Isolated kidneys from Wistar rats were perfused with Krebs-Henseleit solution containing 6% bovine serum albumin. We analyzed renal perfusion pressure (PP), renal vascular resistance (RVR), glomerular filtration rate (GFR), urinary flow (UF), and the percentages of sodium and potassium tubular transport (%TNa+, %TK+). The B. erythromelas venom (10 microg mL(-1)) decreased the PP (ct = 108.71+/-5.09 mmHg; BE = 65.21+/-5.6 mmHg*) and RVR (ct = 5.76+/-0.65 mmHg mL(-1) g(-1) min(-1); BE = 3.10+/-0.45 mmHg mL(-1) g(-1) min(-1)). On the other hand, the GFR decreased at 60 min (ct60 = 0.76+/-0.07 mL g(-1) min(-1); BE60 = 0.42+/-0.12 mL g(-1) min(-1)) and increased at 120 min (ct120 = 0.72+/-0.01 mL g(-1) min(-1); BE120 = 1.24+/-0.26 mL g(-1) min(-1)). The UF increased significantly when compared with the control group (ct = 0.14+/-0.01 mL g(-1) min(-1); BE = 0.47+/-0.08 mL g(-1) min(-1)). The venom reduced the %TNa(+) (ct90 = 79.18+/-0.88%; BE90 = 58.35+/-4.86%) and %TK+ (ct90 = 67.20+/-4.04%; BE90 = 57.32+/-5.26%) The anti-bothropic factor from D. marsupialis (10 microg mL(-1)) incubated with B. erythromelas venom (10 microg mL(-1)) blocked the effects on PP, RVR, %TNa+, and %TK+, but was not able to reverse the effects in UF and GFR promoted by venom alone. However, the highest concentration of D. marsupialis serum (30 microg mL(-1)) reversed all the renal effects induced by the venom. In conclusion, B. erythromelas venom altered all the renal functional parameters evaluated and the anti-bothropic factor from D. marsupialis was able to inhibit the effects induced by the venom in isolated kidney.
急性肾衰竭是巴西蛇咬伤致死病例中最常见的并发症。在巴西的毒蛇中，红口蝮（Bothrops erythromelas）是巴西东北部大多数蛇咬事故的罪魁祸首。负鼠（Didelphis marsupialis）血清可以抑制蛇咬所致中毒的肌坏死、出血、致水肿性痛觉过敏和致死作用。在本研究中，我们评估了从负鼠中分离出的抗红口蝮因子对红口蝮毒液引起的肾脏效应的作用，且无全身干扰。用含6%牛血清白蛋白的Krebs-Henseleit溶液灌注Wistar大鼠的离体肾脏。我们分析了肾灌注压（PP）、肾血管阻力（RVR）、肾小球滤过率（GFR）、尿流率（UF）以及钠和钾的肾小管转运百分比（%TNa+、%TK+）。红口蝮毒液（10μg mL-1）使PP降低（对照组=108.71±5.09 mmHg；毒液组=65.21±5.6 mmHg*）以及RVR降低（对照组=5.76±0.65 mmHg mL-1 g-1 min-1；毒液组=3.10±0.45 mmHg mL-1 g-1 min-1*）。另一方面，GFR在60分钟时降低（对照组60分钟=0.76±0.07 mL g-1 min-1；毒液组60分钟=0.42±0.12 mL g-1 min-1*），而在120分钟时升高（对照组120分钟=0.72±0.01 mL g-1 min-1；毒液组120分钟=1.24±0.26 mL g-1 min-1*）。与对照组相比UF显著增加（对照组=0.14±0.01 mL g-1 min-1；毒液组=0.47±0.08 mL g-1 min-1*）。毒液降低了%TNa+（对照组90分钟=79.18±0.88%；毒液组90分钟=58.35±4.86%）和%TK+（对照组90分钟=67.20±4.04%；毒液组90分钟=57.32±5.26%）。来自负鼠的抗红口蝮因子（10μg mL-1）与红口蝮毒液（10μg mL-1）共同孵育可阻断对PP、RVR、%TNa+和%TK+的影响，但无法逆转毒液单独引起的UF和GFR的变化。然而，最高浓度的负鼠血清（30μg mL-1）可逆转毒液诱导的所有肾脏效应。总之，红口蝮毒液改变了所有评估的肾脏功能参数，来自负鼠的抗红口蝮因子能够抑制毒液对离体肾脏的诱导作用。
