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In vivo metabolism of CCl sub 4 by gerbils pretreated with chlordecone, phenobarbital, or mirex

Conference · · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)
OSTI ID:5678377
;  [1]
  1. Univ. of Mississippi, Jackson (United States)
Gerbils are known to be much more sensitive to CCl{sub 4} lethality than rats as indicated by 48 hours LD{sub 50} (0.08 vs 2.8 ml/kg). On the other hand, gerbils are refractory to chlordecone (CD) potentiation of CCl{sub 4} toxicity. To investigate the possible mechanism underlying gerbil's high sensitivity to CCl{sub 4} lethality, the authors studied in vivo metabolism of CCl{sub 4} in gerbils pretreated with dietary CD (10 ppm), phenobarbital (PB, 225 ppm) or mirex (M, 10 ppm). The hepatic content of CCl{sub 4}, the expiration of {sup 14}CCl{sub 4} and {sup 14}CCl{sub 4}-derived Co{sub 2}, and lipid peroxidation were measured and the results were compared with our previous data for rats. After 15-day dietary pretreatment, male gerbils (60-80 g) received {sup 14}CCl{sub 4} (80 ml/kg; sp act: 0.04 mCi/mmol) ip in corn oil and the expired air was collected for 6 hours. More than 80% of the dose administered was expired as parent compound in 6 hours regardless of pretreatments. Expiration of {sup 14}CCl{sub 4} derived {sup 14}CO{sub 2} in control gerbils was 3.5-fold more than in control rats and was increased significantly in pretreated gerbils (M>PB>CD). PB and M pretreatments resulted in significant increase of {sup 14}C label bound to non-lipid fraction of hepatic content as compared with CD or control gerbils. The radiolabel present in hepatic content of control gerbils was 5-fold higher than that of control rats. In vivo liquid peroxidation measured as diene conjugation in lipid extracts from the livers was lower in gerbils than in rats, and there were no significant differences among control and pretreated gerbils. These data indicate that the more extensive metabolism of CCl{sub 4} in gerbils may partially explain their high sensitivity to CCl{sub 4} toxicity. However, the significantly enhanced metabolism of CCl{sub 4} found in CD, PB, or M pretreated gerbils did not lead to amplification of CCl{sub 4} hepatotoxic and lethal effects.
OSTI ID:
5678377
Report Number(s):
CONF-9004153--
Conference Information:
Journal Name: FASEB Journal (Federation of American Societies for Experimental Biology); (United States) Journal Volume: 4:3
Country of Publication:
United States
Language:
English

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