Specificity of chlordecone-induced potentiation of carbon tetrachloride hepatotoxicity
Curtis, L.R.; Mehendale, H.M.
Drug Metabolism and Disposition the Biological Fate of Chemicals 8(1): 23-27
1980
ISSN/ISBN: 0090-9556 PMID: 6153597 Document Number: 167715
Following a 15-day dietary exposure of male rats to 10 ppm of chlordecone, mirex or photomirex, the hepatotoxicity of CCl4 (0.05 ml/kg, i.p.) was investigated, as was their disposition in liver and bile. Phenobarbital pretreatment (225 ppm for 15 days) served as a positive control of potentiated CCl4 hepatotoxicity. Twenty-four hours after CCl4 administration, rats fed chlordecone exhibited 18- and 14-fold increases in respective serum glutamic-oxalacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) activities, an 88% decrease in biliary excretion of phenol-3,6-dibromophthalein sulfonate, and a 69% decrease in bile flow. Phenobarbital/CCl4 treatment increased SGPT 12-fold and SGOT 6-fold, decreased biliary excretion of phenol-3,6-dibromophthalein sulfonate by 34%, but did not affect bile flow significantly. The pretreatments alone or mirex/CCl4 or photomirex/CCl4 combinations did not alter any of the above parameters of hepatic function. The liver concentration of chlordecone was twice that of mirex and photomirex, whereas the biliary content was 20-fold higher in the absence of CCl4 challenge and 10-fold higher with CCl4. Chlordecone, on a molar basis, is approximately 2 orders of magnitude more potent than phenobarbital in regard to potentiation of CCl4 hepatotoxicity. The chlordecone analogs mirex and photomirex do not share this property, although all 3 agents are inducers of hepatic mixed-function oxidases.