Carbon tetrachloride metabolism in partially hepatectomized and sham‐operated rats pre‐exposed to chlordecone (kepone)

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Abstract
The potentiation of CCl4 toxicity by pre‐exposure to chlordecone (CD) is well established. Chlordecone‐induced metabolism of CCl4 and suppressed hepatocellular repair have been offered as possible mechanisms for this potentiation. Recent work using the partially hepatectomized (PH) rat as a model for an actively regenerating liver has provided supportive evidence for the latter hypothesis. The 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. Male 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. Another group of CD‐pretreated rats received 0.9% CoCl2 (60 mg/kg, sc, qd for 2 days) in lieu of the surgical procedure. On day 16 the rats were challenged with a single dose of CCl4 (100 μL/kg, ip) containing 20 μCi 14CCl4. A radiolabel inventory consisting of exhaled 14CCl4, 14CO2 production, total hepatic 14C, free 14CCl4 and covalently bound 14C was taken over a 6‐hr time period. Lipid peroxidation and serum enzyme activities [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] were measured as indices of toxicity. Neither CD pretreatment alone nor CoCl2 treatment alone produced significant alterations in metabolism of low dose (100 μl/kg) CCl4. No significant difference in 14CCl4 recovery or 14CO2 production was detected for PH versus SH rats. Hepatic 14CCl4‐derived 14C (per gram tissue) was greater in PH rats. Values for free 14CCl4, covalently bound 14C, and lipid peroxidation were similar for SH and PH rats. The data suggest that metabolism and disposition of CCl4 are not altered by PH. Thus 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.