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Chlordecone potentiation of CCl4 hepatotoxicity in ovariectomized rats
Authors:A K Agarwal  H M Mehendale
Affiliation:Cancer Research Unit, University of York, Heslington, York Y01 5DD United Kingdom
Abstract:
Previous reports from this laboratory have established the propensity of chlordecone to potentiate the hepatotoxicity and lethality in male and female rats. The present study was designed to investigate the hepatotoxicity of CCl4 in chlordecone (CD) pretreated, ovariectomized rats. Ten days after bilateral ovariectomy, the rats were maintained on a dietary protocol of either 0 or 10 ppm chlordecone and on the day 15, they received a single i.p. injection of either corn oil (1 ml/kg) or 25 microliter CCl4/kg in corn oil. Hepatic function, serum enzyme levels and histopathological changes were assessed 24 h after CCl4 challenge as functional biochemical, and morphological parameters of hepatotoxicity. Hepatobiliary function was markedly impaired and serum enzyme levels were elevated in ovariectomized rats receiving the same treatment but not significantly different from normal females receiving the chlordecone and CCl4 combination. Histological findings indicated a greater degree of centrilobular hepatic necrosis accompanied by extensive fatty infiltration. This study suggests that chlordecone sensitizes the liver in ovariectomized rats as well to amplify the toxic effects of CCl4.
Keywords:Benzidine azodyes  DNA binding  DNA-adduct analysis  H acid  1-naphthol-8-amino-3,6-disulphonic acid  SDS  sodium dodecyl sulphate  HPLC  high pressure liquid chromatography  P450  To whom correspondence should be addressed.
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