Rothkopf M, Vogel G, Lang W, Leng E
Arzneimittelforschung. 1977;27(3):598-605.
The possibility that aescin might have a nephrotoxic side effect has been investigated by clearance studies in kidneys of healthy rats and by toleration studies in rats with damaged kidneys. The effect of aescin, both free and albumin-bound, on renal tubular transport processes was studied in the model of the isolated, artificially perfused frog kidney. The rates at which different concentrations of aescin were bound to rat plasma proteins were determined in vitro. The clearance of i.v. aescin was 13% of creatinine clearance and 7% of p-aminohippurate (PAH) clearance; this rules out the tubular secretion of aescin. No deaths occurred among aminonucleoside-damaged rats given i.v. sodium aescinate 2.2 mg/kg, but rats damaged with mercuric chloride or uranyl nitrate had exactly the same mortality rate as those given 2.2 mg/kg i.v. of sodium aescinate alone. The rats received four injections in all of aescin 0.35 mg/kg i.v., given at intervals of two days. Aescin had no effect on renal damage caused by aminonucleoside, mercuric chloride or uranyl nitrate. Aescin concentrations of 0.2 mg/l and 2.0 mg/l in the perfusion fluid increased the excretion of Na+ and glucose by the frog kidney and reduced the reabsorption of both these substances. With a sodium aescinate concentration of 5 mg/l the production of urine ceased. When 1% (w/v) of albumin was added to the perfusion fluid, even sodium aescinate 5 mg/l had no effect on the tubular transport of Na+, glucose and water. The fact that about 50% of aescin was not bound to plasma protein in vitro suggests that some of the small amount of aescin in the glomerular filtrate is reabsorbed in the tubules.
通过对健康大鼠肾脏的清除率研究以及对肾损伤大鼠的耐受性研究,已对七叶皂苷可能具有肾毒性副作用的可能性进行了调查。在离体人工灌注蛙肾模型中,研究了游离型和白蛋白结合型七叶皂苷对肾小管转运过程的影响。体外测定了不同浓度七叶皂苷与大鼠血浆蛋白的结合率。静脉注射七叶皂苷的清除率为肌酐清除率的13%,对氨基马尿酸(PAH)清除率的7%;这排除了七叶皂苷的肾小管分泌。给予静脉注射2.2mg/kg七叶皂苷钠的氨基核苷损伤大鼠中没有死亡,但氯化汞或硝酸铀酰损伤的大鼠与仅静脉注射2.2mg/kg七叶皂苷钠的大鼠死亡率完全相同。大鼠总共接受了4次静脉注射,每次0.35mg/kg七叶皂苷,间隔两天给药。七叶皂苷对氨基核苷、氯化汞或硝酸铀酰引起的肾损伤没有影响。灌注液中七叶皂苷浓度为0.2mg/l和2.0mg/l时,可增加蛙肾Na+和葡萄糖的排泄,并减少这两种物质的重吸收。当七叶皂苷钠浓度为5mg/l时,尿液生成停止。当向灌注液中加入1%(w/v)的白蛋白时,即使是5mg/l的七叶皂苷钠对Na+、葡萄糖和水的肾小管转运也没有影响。体外约50%的七叶皂苷不与血浆蛋白结合这一事实表明,肾小球滤液中少量的七叶皂苷有些会在肾小管中被重吸收。