Martines Monique Silva, Mendes Mirian M, Shimizu Maria H M, Melo Rodrigues Veridiana, de Castro Isac, Filho Sebastião R Ferreira, Malheiros Denise M A C, Yu Luis, Burdmann Emmanuel A
LIM 12, Division of Nephrology, University of Sao Paulo Medical School, São Paulo, São Paulo, Brazil.
Biological Science Institute, Goias Federal University, Jataí, Goiás, Brazil.
PLoS One. 2014 Feb 14;9(2):e86828. doi: 10.1371/journal.pone.0086828. eCollection 2014.
Venom-induced acute kidney injury (AKI) is a frequent complication of Bothrops snakebite with relevant morbidity and mortality. The aim of this study was to assess the effects of Schizolobium parahyba (SP) extract, a natural medicine with presumed anti-Bothrops venom effects, in an experimental model of Bothrops jararaca venom (BV)-induced AKI.
Groups of 8 to 10 rats received infusions of 0.9% saline (control, C), SP 2 mg/kg, BV 0.25 mg/kg and BV immediately followed by SP (treatment, T) in the doses already described. After the respective infusions, animals were assessed for their glomerular filtration rate (GFR, inulin clearance), renal blood flow (RBF, Doppler), blood pressure (BP, intra-arterial transducer), renal vascular resistance (RVR), urinary osmolality (UO, freezing point), urinary neutrophil gelatinase-associated lipocalin (NGAL, enzyme-linked immunosorbent assay [ELISA]), lactate dehydrogenase (LDH, kinetic method), hematocrit (Hct, microhematocrit), fibrinogen (Fi, Klauss modified) and blinded renal histology (acute tubular necrosis score).
BV caused significant decreases in GFR, RBF, UO, HcT and Fi; significant increases in RVR, NGAL and LDH; and acute tubular necrosis. SP did not prevent these changes; instead, it caused a significant decrease in GFR when used alone.
SP administered simultaneously with BV, in an approximate 10∶1 concentration, did not prevent BV-induced AKI, hemolysis and fibrinogen consumption. SP used alone caused a decrease in GFR.
蛇毒诱导的急性肾损伤(AKI)是具窍蝮蛇咬伤常见的并发症,具有相关的发病率和死亡率。本研究的目的是在具窍蝮蛇蛇毒(BV)诱导的AKI实验模型中评估具有假定抗具窍蝮蛇蛇毒作用的天然药物裂叶豆提取物(SP)的效果。
将8至10只大鼠分为几组,分别给予0.9%生理盐水(对照组,C)、2mg/kg的SP、0.25mg/kg的BV以及先给予BV后立即给予SP(治疗组,T),剂量如前所述。在各自输注后,评估动物的肾小球滤过率(GFR,菊粉清除率)、肾血流量(RBF,多普勒)、血压(BP,动脉内传感器)、肾血管阻力(RVR)、尿渗透压(UO,冰点)、尿中性粒细胞明胶酶相关脂质运载蛋白(NGAL,酶联免疫吸附测定[ELISA])、乳酸脱氢酶(LDH,动力学方法)、血细胞比容(Hct,微量血细胞比容)、纤维蛋白原(Fi,改良克劳斯法)以及进行盲法肾组织学检查(急性肾小管坏死评分)。
BV导致GFR、RBF、UO、Hct和Fi显著降低;RVR、NGAL和LDH显著升高;并出现急性肾小管坏死。SP未能预防这些变化;相反,单独使用时会导致GFR显著降低。
以约10∶1的浓度与BV同时给予SP,不能预防BV诱导的AKI、溶血和纤维蛋白原消耗。单独使用SP会导致GFR降低。