Comparative changes in hepatic DNA, RNA, protein, lipid, and glycogen induced by a subtoxic dose of CCl4 in chlordecone, mirex, and phenobarbital pretreated rats.
Male Sprague-Dawley rats (200-250 g) were maintained on a normal powdered diet or on a similar diet containing 10 ppm chlordecone (CD), 10 ppm mirex (M) or 225 ppm phenobarbital (PB) for 15 days. On day 15, the animals received a single i.p. administration of CCl4 (100 microliters/kg). Hepatic DNA, RNA, protein, lipid and glycogen were determined 1, 4, 6, 12, 24 and 36 h after CCl4 administration. A significant decrease (18%) in hepatic protein was observed 24 h after CCl4 challenge in the CD-pretreated rats; significant changes were not observed in the other treatment groups. Hepatic RNA was decreased (37%) in CD-pretreated rats at 36 h; no changes were observed in the DNA content. Hepatic RNA and DNA were increased (20% and 16%, respectively) 6 h after exposure to CCl4 alone. Lipid content was increased at all time points starting at 4 h in response to CCl4 challenge in the CD-pretreated rats. In the M- and PB-pretreated rats increases in hepatic lipid (22 and 28%, respectively) were observed only at the 6-h time point. Only a transient increase occurred after CCl4 alone at 4 h. While depletion of hepatic glycogen was manifested in all groups at all time points following CCl4, that in the CD + CCl4 group was the greatest. A recovery of glycogen beginning at 12 h was observed in the rats receiving CCl4 alone and in the M and PB pretreated animals. No such recovery was evident in CD + CCl4 group. These studies indicate that biochemical changes compatible with cellular death are more pronounced in the CD-pretreated rats than in those receiving CCl4 alone, suggesting that the metabolic and supportive biochemical mechanisms for hepatocellular repair are suppressed in rats receiving CD + CCl4.
D000818:Animals; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D007631:Chlordecone / Q000494:pharmacology*; D004247:DNA / Q000032:analysis; D007306:Insecticides / Q000494:pharmacology*; D008055:Lipids / Q000032:analysis; D008099:Liver / Q000032:analysis / Q000187:drug effects*; D008112:Liver Glycogen / Q000032:analysis; D008297:Male; D008917:Mirex / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology*; D011506:Proteins / Q000032:analysis; D012313:RNA / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains
D007306:Insecticides; D008055:Lipids; D008112:Liver Glycogen; D011506:Proteins; D012313:RNA; D004247:DNA; D002251:Carbon Tetrachloride; D007631:Chlordecone; D010634:Phenobarbital; D008917:Mirex