Comparative changes in hepatic DNA, RNA, protein, lipid, and glycogen induced by a subtoxic dose of CCl 4 in chlordecone, mirex, and phenobarbital pretreated rats

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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 CCl 4 (100 μ kg ). Hepatic DNA, RNA, protein, lipid and glycogen were determined 1, 4, 6, 12, 24 and 36 h after CCl 4 administration. A significant decrease (18 %) in hepatic protein was observed 24 h after CCl 4 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 CC1 4 alone. Lipid content was increased at all time points starting at 4 h in response to CCl 4 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 CCl 4 alone at 4 h. While depletion of hepatic glycogen was manifested in all groups at all time points following CCl 4, that in the CD + CCl 4 group was the greatest. A recovery of glycogen beginning at 12 h was observed in the rats receiving CCl 4 alone and in the M and PB pretreated animals. No such recovery was evident in CD + CCl 4 group. These studies indicate that biochemical changes compatible with cellular death are more pronounced in the CD-pretreated rats than in those receiving CCl 4 alone, suggesting that the metabolic and supportive biochemical mechanisms for hepatocellular repair are suppressed in rats receiving CD + CCl 4.