Chlordecone does not interfere with hepatic repair after carbon tetrachloride or partial hepatectomy.
The effect of chlordecone (CD) on hepatic repair, measured either as recovery of microsomal enzymatic functions or as the induction of cytosolic thymidine kinase (TK) activity, was evaluated in rats given carbon tetrachloride (CCl4). Carbon tetrachloride was administered to CD-potentiated and control animals using doses of this hepatotoxin which produce similar degrees of damage at 24 hours in both groups of animals (6 and 100 microliters CCl4 per 100 g body weight, respectively). Chlordecone had no significant effect on the time course of recovery of microsomal cytochrome P-450 content or glucose-6-phosphatase activity following CCl4 administration. Hepatic TK activity was measured 48 hours after CCl4 administration as a biochemical index of the hepatic regenerative response. Thymidine kinase activity was increased eightfold in CD-treated rats receiving 6 microliters CCl4 per 100 g body weight, whereas in controls a similar induction of TK activity was produced by 100 microliters CCl4 per 100 g body weight. Therefore, the TK response in CD-treated rats receiving CCl4 is appropriate for the amount of damage produced, suggesting that CD does not inhibit the hepatic regenerative response to CCl4-induced injury. The effect of CD on hepatic repair was also examined in rats receiving a two-thirds partial hepatectomy. Pretreatment of animals with CD had no significant effect on the increase in TK activity produced 24 hours after partial hepatectomy. These results offer no support for the idea that CD impairs hepatic repair after either partial hepatectomy or CCl4 administration.
Dolak
J A
JA
Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106.
Britton
R S
RS
Glende
E A
EA
Recknagel
R O
RO
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D007631:Chlordecone / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D004790:Enzyme Induction / Q000187:drug effects; D005952:Glucose-6-Phosphatase / Q000032:analysis / Q000378:metabolism; D006498:Hepatectomy; D007306:Insecticides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013937:Thymidine Kinase / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism
D007306:Insecticides; D003577:Cytochrome P-450 Enzyme System; D002251:Carbon Tetrachloride; D013937:Thymidine Kinase; D005952:Glucose-6-Phosphatase; D007631:Chlordecone