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CARBON TETRACHLORIDE METABOLISM IN PARTIALLY HEPATECTOMIZED AND SHAM OPERATED RATS PRE-EXPOSED TO CHLORDECONE (KEPONE R)1
Citation:
Young, R. AND H. Mehendale. CARBON TETRACHLORIDE METABOLISM IN PARTIALLY HEPATECTOMIZED AND SHAM OPERATED RATS PRE-EXPOSED TO CHLORDECONE (KEPONE R)1. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-89/464 (NTIS PB91109553), 1989.
Description:
The potentiation of CCl4 toxicity by preexposure to chlordecone (CD) is well established. hlordecone-induced metabolism of C14 and suppressed hepatocellular repair have been offered as possible mechanisms for this potentiation. ecent work using the partially hepatectomized (PH) rat as a model for an actively regenerating liver has provided supportive evidence for the latter hypothesis. he present study was initiated to determine if metabolism and disposition of 14CCl4 is altered in the PH rat, and if this is a contributing factor to the reported protective effect afforded by the PH procedure. ale Sprague-Dawley rats (150-175 g) maintained on dietary CD (10 ppm) for 15 days were partially hepatectomized or sham-operated (SH) on day 15. nother group of CD-pretreated rats received 0.9% CoCl2 (60 mg/kg, sc, qd for 2 days) in lieu of the surgical procedure. n day 16 the rats were challenged with a single dose of CCl4 (100 uL/kg, ip) containing 20 uCi 14CCl. adiolabel inventory consisting of exhaled 14 CCl4, 14CO2 production, total hepatic 14C, free 14CCl4 and covalently bound 14C was taken over a 6-hr time period. ipid peroxidation and serum enzyme activities (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured as indices of toxicity. either CD pretreatment alone nor CoCl2 treatment along produced significant alternations in metabolism of low dose (100 ul/kg) CCl4. o significant differences in 14CCl4, covalently bound 14C, and lipid peroxidation were similar for SH and PH rats. he data suggest that metabolism and disposition of CCl4 are not altered by PH. hus the PH rat is a valid model for studying the CD + CCl4 interaction in an actively regenerating liver, and the protection afforded by partial hepatectomy is not due to a reduction in hepatic uptake or bioactivation of CCl4.
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CARBON TETRACHLORIDE METABOLISM IN PARTIALLY HEPATECTOMIZED AND SHAM OPERATED RATS PRE-EXPOSED TO CHLORDECONE (KEPONE R)1