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© 1989 Oxford University Press

research-article

Effect in the Rat of the Interaction of Dichloromaleic Acid and Carbon Tetrachloride on Renal and Hepatic Function

W. R. CHRISTENSON*, M. E. DAVIS{dagger} and W. O. BERNDT*

*Department of Pharmacology. College of Medicine, University of Nebraska Medical Center, 42nd and Dewey A venue Omaha, Nebraska 68105 {dagger}Department of Pharmacology and Toxicology, Health Sciences Center, West Virginia University Morganlown, West Virginia 26506

Received January 19, 1989; accepted February 10, 1989

Water purification generates a vanety of chlorinated contaminants, one of which is dichloromaleic acid (DCMA). Exposure to this compound is likely to occur in combination with other drinking water pollutants, some of which are hepatotoxic. This study was designed to examine the interactive effects of carbon tetrachioride (CCl4)a a known hepatotoxin, with DCMA on liver and kidney function in the Sprague-Dawley rat. Administration of a single dose of DCMA (200–400 mg/kg, ip) caused modest dose-dependent increases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and plasma urea nitrogen, as well as a marked depletion of nonprotein sulfhydryls (NPSH) in the liver, but not the kidney, by 24 hr. Pretreatment with inducers (phenobarbital or 3-methylcholanthrene) or an inhibitor (SKF 525A) of cytochrome P-450 activity failed to alter the response observed with DCMA alone. Alterations in 24-hr urine volume, osmolality, and water consumption also were observed. DCMA-mediated changes in plasma urea nitrogen and NPSH were reduced in magnitude with coadministration of CCl4 (1 ml/kg, ip), while anticipated CCl4-induced increases in ALT and AST were reduced with coexposure to DCMA. Renal slice expenments indicated that DCMA-treated rats were less able to accumulate the organic anion p-aminohippurate (PAH), whereas DCMA had no effect on accumulation of the organic cation tetraethylammonium (TEA). The combination of CCl4. and DCMA produced only additive effects on organicion accumulation. These results suggest hepatic interaction possibly related to the metabolism of CCl4 and DCMA, resulting in renal and hepatic toxicity diminished from that observed with exposure to either agent alone.


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