Role of hepatocellular regeneration in chlordecone potentiated hepatotoxicity of carbon tetrachloride.
Previous histomorphometric studies led us to hypothesize that suppression of hepatocellular regeneration and the repair of the hepatolobular architecture was involved besides bioactivation phenomenon in the progressive and irreversible phase of toxicity resulting from CD + CCl4 interaction. We have recently observed significant protection from CD potentiated CCl4 toxicity in animals which are stimulated for active hepatocellular regeneration. The present work is an extension of our earlier histomorphometric investigation, taking 3H-thymidine (3H-T) incorporation as a biochemical parameter to assess hepatocellular regeneration followed by autoradiographic analysis of liver sections in normal (N) or chlordecone (CD) treated (10 ppm in diet for 15 days) male rats undergoing sham (SH) or partial hepatectomies (PH). Initial experiments established that in normal (N) rats, greatest 3H-T incorporation into hepatocellular nuclear DNA occurs at 2 days post-PH which returns to basal levels by 7 days. CD treatment alone did not change this phenomenon. 3H-T incorporation into nuclear DNA and the percentage of labelled cells as evidenced by autoradiography of liver sections were significantly elevated in N rats at 1-2 h after CCl4 (100 microliters/kg) administration and returned to basal level by 6 h. Serum enzymes (AST and ALT) in N rats undergoing SH and PH were not altered, but were significantly elevated in CD rats following CCl4 (100 microliters/kg) administration. CCl4-induced serum enzyme elevations were significantly lower in 2 days post-PH (PH2) rats when compared to SH rats or 7 days post-PH (PH7) rats maintained on CD diet, indicating that CD potentiated CCl4 hepatotoxicity is significantly reduced in livers stimulated for regenerative activity by PH.(ABSTRACT TRUNCATED AT 250 WORDS)
Kodavanti
P R
PR
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505.
Joshi
U M
UM
Young
R A
RA
Bell
A N
AN
Mehendale
H M
HM
D000818:Animals; D001345:Autoradiography; D002252:Carbon Tetrachloride Poisoning / Q000201:enzymology / Q000503:physiopathology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000503:physiopathology*; D007631:Chlordecone / Q000633:toxicity*; D004247:DNA / Q000096:biosynthesis; D004032:Diet; D004357:Drug Synergism; D006498:Hepatectomy; D007306:Insecticides; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013936:Thymidine / Q000378:metabolism
D007306:Insecticides; D004247:DNA; D007631:Chlordecone; D013936:Thymidine