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Chlordecone (kepone®)‐potentiated carbon tetrachloride hepatotoxicity in partially hepatectomized rats — a histomorphometric study
Author(s) -
Kodavanti Prasada Rao S.,
Joshi Urmila M.,
Mehendale Harihara M.,
Lockard Virginia G.
Publication year - 1989
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2550090602
Subject(s) - carbon tetrachloride , toxicity , chemistry , liver regeneration , ccl4 , in vivo , regeneration (biology) , pharmacology , mitosis , medicine , endocrinology , biology , microbiology and biotechnology , organic chemistry
Our previous studies indicated the involvement of some unidentified mechanisms, apart from the bioactivation phenomenon, in chlordecone (CD)‐potentiated CCl 4 hepatotoxicity and lethality. Recent studies revealed that hepatocellular regeneration is suppressed in CD + CCl 4 toxicity. The present work is a continuation of our earlier work employing a partial hepatectomy model for stimulating hepatocellular division, in normal (N) or CD‐treated (10 ppm for 15 days) rats. Male Sprague‐Dawley rats maintained on an appropriate dietary protocol and undergoing sham (SH) or partial hepatectomies (PH) were employed. Hepatocellular regeneration was assessed by measuring the percentage mitotic figures and by autoradiography of liver sections from rats given 3 H‐thymidine in vivo . Hepatotoxicity was assessed by examining liver sections for necrotic cells, swollen cells and cells having lipid droplets. CCl 4 (100 μl kg −1 )‐induced histopathological alterations in CD‐pretreated rats were significantly decreased in rats 2 days post‐PH (PH 2 ) as compared to SH rats or rats 7 days post‐PH (PH 7 ), indicating that amplification of CCl 4 toxicity is significantly reduced when there is a greater regenerative activity. The percentage of mitoses as well as the percentage of labelled cells were significantly elevated at 2–6 h after CCl 4 administration in N rats but remained suppressed in CD rats. In CD‐pretreated PH 2 rats where the percentage of mitoses and the percentage of labelled cells were many‐fold greater when compared to SH or PH 7 rats, a portion of the stimulated hepatocellular division decreased significantly at 2–6 h after CCl 4 administration, but remained significantly greater when compared to basal level of regeneration. These results support our concept that suppression of hepatocellular regeneration is one of the events responsible, besides the bioactivation phenomenon, for the CD‐potentiated CCl 4 hepatotoxicity.