Christenson W R, Davis M E, Berndt W O
Department of Pharmacology, College of Medicine, University of Nebraska Medical Center, Omaha 68105.
Toxicol Lett. 1989 Oct;49(1):21-7. doi: 10.1016/0378-4274(89)90096-9.
Subthreshold doses of potassium dichromate (K2Cr2O7) have been shown to enhance or potentiate the nephrotoxic effects of mercuric chloride and citrinin. The mechanism of this effect is unknown. The purpose of this study was to examine the phenomenon further by investigating the interaction of K2Cr2O7 with maleic acid, a nephrotoxicant with an action though to be different from those above. Male rats were housed in stainless steel metabolism cages and received a single intraperitoneal injection of maleic acid (300 mg/kg). K2Cr2O7 (10 mg/kg s.c.) or the combination of maleic acid plus K2Cr2O7. While treatment with either agent alone produced only minimal alterations in renal function, the combination of agents produced marked changes in 24 h urine volume, glucose excretion and osmolality. Water consumption was unaffected by the combined treatment. A marked decline in the capacity of renal slices to accumulate both organic anions (p-aminohippurate) and cations (tetraethylammonium) was observed after treatment with both substances. Modifications in renal and hepatic non-protein sulfhydryl content also were observed. These results suggest that K2Cr2O7, as was observed with both mercury and citrinin, enhanced or potentiated the nephrotoxic effects of maleic acid, probably in the proximal tubule, the principal site of glucose reabsorption and organic ion secretion.
已表明，亚阈值剂量的重铬酸钾（K2Cr2O7）可增强或强化氯化汞和桔霉素的肾毒性作用。这种作用的机制尚不清楚。本研究的目的是通过研究K2Cr2O7与马来酸的相互作用来进一步探讨这一现象，马来酸是一种肾毒物，其作用方式据认为与上述物质不同。将雄性大鼠饲养在不锈钢代谢笼中，单次腹腔注射马来酸（300mg/kg）、K2Cr2O7（10mg/kg皮下注射）或马来酸加K2Cr2O7的组合。虽然单独使用任何一种药物治疗仅对肾功能产生最小的改变，但药物组合却使24小时尿量、葡萄糖排泄和渗透压发生了显著变化。联合治疗对水的消耗没有影响。在用两种物质治疗后，观察到肾切片积累有机阴离子（对氨基马尿酸）和阳离子（四乙铵）的能力显著下降。还观察到肾和肝非蛋白巯基含量的改变。这些结果表明，与汞和桔霉素一样，K2Cr2O7增强或强化了马来酸的肾毒性作用，可能是在近端小管，即葡萄糖重吸收和有机离子分泌的主要部位。
