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

✍ Scribed by Young, Robert A. ;Mehendale, Harihara M.

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: English
• Weight: 833 KB
• Volume: 4
• Category: Article
• ISSN: 0887-2082
• DOI: 10.1002/jbt.2570040403

✦ Synopsis

The potentiation of CC14 toxicity by preexposure to chlordecone (CD) is well established. Chlordecone-induced metabolism of C C 4 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 l4Ccl4 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% CoC12 (60 mglkg, sc, qd for 2 days) in lieu of the surgical procedure. On day 16 the rats were challenged with a single dose of CC14 (100 pLlkg, ip) containing 20 pCi l4Ccl4. A radiolabel inventory consisting of exhaled l4Ccl4, 14C02 production, total hepatic 14C, free l4Ccl4 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 CoC12 treatment alone produced significant alterations in metabolism of low dose (100 pllkg) CC14. No significant difference in l4Ccl4 recovery or 14C02 production was detected for PH versus SH rats. Hep-~ ~