Effect in the Rat of the Interaction of Dichloromaleic Acid and Carbon Tetrachloride on Renal and Hepatic Function.
NEBRASKA UNIV MEDICAL CENTER OMAHA DEPT OF PHARMACOLOGY
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Water purification generates a variety of chlorinated contaminants, one of which is dischloromaleic 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 tetrachloride CCI4, a known hepatotoxin, with DCMA on liver and kidney function in the Sprague-Dawley rat. Administration of a single dose of DCMA 200-400 mgkg, 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.