Carbon tetrachloride metabolism in partially hepatectomized and sham-operated rats pre-exposed to chlordecone (Kepone).
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 14CC14 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 microL/kg, ip) containing 20 muCi 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 in indices of toxicity. Neither CD pretreatment alone nor CoCl2 treatment alone produced significant alterations in metabolism of low dose (100 microliters/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.(ABSTRACT TRUNCATED AT 250 WORDS)
Young
R A
RA
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216.
Mehendale
H M
HM
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002245:Carbon Dioxide / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000378:metabolism*; D007631:Chlordecone / Q000633:toxicity*; D004357:Drug Synergism; D006498:Hepatectomy; D007306:Insecticides / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012588:Scintillation Counting; D013997:Time Factors
D007306:Insecticides; D002245:Carbon Dioxide; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D007631:Chlordecone