Christenson W R, Davis M E, Berndt W O
Department of Pharmacology, College of Medicine, University of Nebraska Medical Center, Omaha 68105.
Toxicology. 1989 Jun 16;56(3):229-38. doi: 10.1016/0300-483x(89)90087-5.
Maleic acid (MA), a known nephrotoxicant in experimental animals, and its chlorinated derivative dichloromaleic acid (DCMA) are present in urban drinking water supplies as by-products of the chlorination process. This study was designed to characterize the effects of simultaneous exposure of subtoxic doses of DCMA and MA on renal function in both sexes of the Sprague-Dawley rat. Urine was collected at 24-h intervals from rats housed individually in stainless steel metabolism cages. Subcutaneous administration of MA at a dose of 150 mg/kg had no effect on several parameters of renal function in either sex at 24 h and only modest effects at 48 h. Renal slice studies showed that treatment of both male and female rats with DCMA (300 mg/kg) reduced p-aminohippurate (PAH) accumulation at 24 h with no effect on the uptake of tetraethylammonium ion (TEA). The combination of MA + DCMA caused a depression of TEA accumulation by slices from the female. Also, changes in urinary glucose excretion and blood urea nitrogen, although additive in the male following coexposure, appeared synergistic or potentiated in the female. These results suggest an enhanced susceptibility of the female rate to the nephrotoxic action of combined exposure to MA and DCMA.
马来酸（MA）是实验动物中一种已知的肾毒性物质，其氯化衍生物二氯马来酸（DCMA）作为氯化过程的副产物存在于城市饮用水供应中。本研究旨在表征亚毒性剂量的DCMA和MA同时暴露对Sprague-Dawley大鼠两性肾功能的影响。从单独饲养在不锈钢代谢笼中的大鼠每隔24小时收集一次尿液。皮下注射剂量为150 mg/kg的MA在24小时时对两性的几个肾功能参数均无影响，在48小时时仅有适度影响。肾切片研究表明，用DCMA（300 mg/kg）处理雄性和雌性大鼠均会在24小时时降低对氨基马尿酸（PAH）的积累，而对四乙铵离子（TEA）的摄取无影响。MA + DCMA组合导致雌性大鼠切片对TEA积累的抑制。此外，尿糖排泄和血尿素氮的变化，虽然在雄性共同暴露后是相加的，但在雌性中似乎是协同的或增强的。这些结果表明雌性大鼠对MA和DCMA联合暴露的肾毒性作用的易感性增强。
