Alterations in the renal function of male and female rats exposed to maleic acid, dichloromaleic acid, and both compounds.
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.
Christenson
W R
WR
Department of Pharmacology, College of Medicine, University of Nebraska Medical Center, Omaha 68105.
Davis
M E
ME
Berndt
W O
WO
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001806:Blood Urea Nitrogen; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006029:Glycosuria / Q000139:chemically induced; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008298:Maleates / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors; D013438:Sulfhydryl Compounds / Q000378:metabolism; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000378:metabolism; D010130:p-Aminohippuric Acid / Q000378:metabolism
D008298:Maleates; D013438:Sulfhydryl Compounds; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; C030272:maleic acid; D010130:p-Aminohippuric Acid