Zalups R K, Gelein R M, Morrow P E, Diamond G L
Department of Pharmacology, University of Rochester Medical Center, New York 14642.
Toxicol Appl Pharmacol. 1988 Jun 15;94(1):11-22. doi: 10.1016/0041-008x(88)90332-8.
The aim of the present study was to determine whether the nephrotoxicity of the uranium-containing compound uranyl fluoride (UO2F2) is enhanced after unilateral nephrectomy. Unilaterally nephrectomized (NPX) and sham-operated (SO) rats were given single intravenous injections of UO2F2 at doses delivering 100 or 250 micrograms U/kg 16 days after surgery. Between the second and third day after the administration of either dose of UO2F2, the urinary excretion of the cellular enzymes lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) and the plasma solute albumin began to increase significantly in both the NPX and SO rats. The urinary excretion of the plasma solute glucose did not begin to increase significantly in the NPX and SO rats until 4 days after the administration of either dose of UO2F2. During the fifth day following the administration of either dose of UO2F2 (which was also the last day that urinary data were collected) the urinary excretion of LDH, AST, and glucose in the NPX and SO rats was greater than that during any previous day. The urinary excretion of these three compounds during this fifth day was greater in the SO rats than in the NPX rats. Also during the fifth day following the injection of either dose of UO2F2, the fractional excretion of glucose was higher in the SO rats than in the NPX rats. By the end of the fifth day, the level of histologically demonstrable cellular necrosis in the pars recta of proximal tubules in the renal cortex and outer medulla of the NPX and SO rats was statistically similar. Therefore, the nephropathy in rats induced by UO2F2 is not made more severe as a result of unilateral nephrectomy.
本研究的目的是确定单侧肾切除术后含铀化合物氟化铀酰(UO₂F₂)的肾毒性是否增强。在手术后16天,对单侧肾切除(NPX)和假手术(SO)的大鼠进行单次静脉注射UO₂F₂,剂量分别为每千克体重输送100或250微克铀。在给予任一剂量的UO₂F₂后的第二天至第三天之间,NPX和SO大鼠的细胞酶乳酸脱氢酶(LDH)和天冬氨酸转氨酶(AST)的尿排泄量以及血浆溶质白蛋白开始显著增加。在给予任一剂量的UO₂F₂后的4天,NPX和SO大鼠的血浆溶质葡萄糖的尿排泄量才开始显著增加。在给予任一剂量的UO₂F₂后的第五天(这也是收集尿液数据的最后一天),NPX和SO大鼠的LDH、AST和葡萄糖的尿排泄量均高于之前的任何一天。在这第五天,SO大鼠的这三种化合物的尿排泄量高于NPX大鼠。同样在注射任一剂量的UO₂F₂后的第五天,SO大鼠的葡萄糖分数排泄率高于NPX大鼠。到第五天结束时,NPX和SO大鼠肾皮质和外髓质近端小管直部的组织学可证实的细胞坏死水平在统计学上相似。因此,UO₂F₂诱导的大鼠肾病不会因单侧肾切除而变得更严重。