Koschier F J, Gigliotti P J, Hong S K
J Environ Pathol Toxicol. 1980 Nov;4(5-6):209-17.
The principle water-soluble metabolite of DDT in mammals has been shown to be DDA (bis(p-chlorophenyl)acetic acid). Previous studies suggested that DDA was secreted by the renal proximal tubule and was reabsorbed at an unspecified site in the nephron. Since DDA has been known to produce alterations in cellular functions, the present study examined the possibility that the renal transport of DDA was capable of causing acute nephrotoxicity. When 100 mg/kg of DDA was infused iv into the rat during a 90 min period, there was a significant decrease (congruent to 20%) in the glomerular filtration rate (GFR) after 110 min from the start of administration. During these experiments, there was no change in the mean arterial blood pressure (MABP), urine flow rate (V), renal clearance of tetraethylammonium (CTEA) or fractional reabsorption of Na (FRNa). After 200 mg/kg of DDA was infused iv into the rat during a 90 min period, there was a 60% decrease in the GFR, CTEA and V. However, the decrease in renal function was accompanied by a dramatic reduction in MABP (125 to 60 mmHg). To determine whether DDA could have produced acute renal failure when the perfusion pressure was kept constant, isolated kidney experiments were performed. In these experiments, DDA (1.0 mM) was present in a dextran perfusate and the perfusion pressure was kept constant at 90 mmHg. During these experiments, the GFR, V and FRNa were decreased significantly. The results indicated that a high perfusate concentration of DDA caused acute renal failure in the isolated kidney which was produced even when the perfusion pressure was kept constant. In conclusion, DDA produced renal failure in vivo which was associated with a reduction in renal perfusion pressure; however, perfused kidney experiments indicated that DDA could have caused a direct effect on nephron function.
滴滴涕（DDT）在哺乳动物体内的主要水溶性代谢产物已被证明是二氯二苯乙酸（DDA，双（对氯苯基）乙酸）。先前的研究表明，DDA由近端肾小管分泌，并在肾单位的某个未明确部位被重吸收。由于已知DDA会引起细胞功能改变，本研究探讨了DDA的肾脏转运是否会导致急性肾毒性的可能性。当在90分钟内给大鼠静脉注射100mg/kg的DDA时，给药开始110分钟后，肾小球滤过率（GFR）显著下降（约20%）。在这些实验过程中，平均动脉血压（MABP）、尿流率（V）、四乙铵的肾清除率（CTEA）或钠的分数重吸收（FRNa）均无变化。当在90分钟内给大鼠静脉注射200mg/kg的DDA时，GFR、CTEA和V下降了60%。然而，肾功能的下降伴随着MABP的显著降低（从125mmHg降至60mmHg）。为了确定在灌注压力保持恒定的情况下DDA是否会导致急性肾衰竭，进行了离体肾实验。在这些实验中，DDA（1.0mM）存在于葡聚糖灌注液中，灌注压力保持恒定在90mmHg。在这些实验过程中，GFR、V和FRNa均显著下降。结果表明，高灌注液浓度的DDA在离体肾中导致了急性肾衰竭，即使灌注压力保持恒定也会发生。总之，DDA在体内导致肾衰竭，这与肾灌注压力降低有关；然而，离体肾实验表明DDA可能对肾单位功能有直接影响。
