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Excretion of chlordecone by the gastrointestinal tract: Evidence for a nonbiliary mechanism
Author(s) -
Boylan J. J.,
Cohn W. J.,
Egle J. L.,
Blanke R. V.,
Guzelian P. S.
Publication year - 1979
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1979255part1579
Subject(s) - enterohepatic circulation , cholestyramine , excretion , duodenum , feces , medicine , chemistry , metabolite , gastrointestinal tract , endocrinology , metabolism , biology , cholesterol , microbiology and biotechnology
Workers exposed to chlordecone (Kepone), a toxic organochlorine pesticide, excreted larger amounts of chlordecone in bile than in stool, suggesting that it may undergo enterohepatic recirculation. We found in a single subject that equal amounts of chlordecone and of its reduced metabolite, chlordecone alcohol, were excreted in bile at a rate four times as great as in stool. When biliary contents were diverted from the intestine through a T tube, fecal excretion of chlordecone alcohol was abolished, presumably due to interruption of its passage via bile to intestine. This change was not accompanied by disappearance of chlordecone from the stool. The amount of chlordecone in stool when bile was diverted was increased six‐ to tenfold over that when diverted bile was continuously infused into the duodenum. Analogous experiments with [ 14 C]‐chlordecone‐treated rats in which bile flow was exteriorized through a plastic cannula showed that the excretion of radioactivity in feces was in the same range when bile was reinfused in the duodenum or was totally diverted. Moreover, in rats with bile diverted, cholestyramine, an anion‐exchange resin which binds chlordecone in vitro, doubled the excretion of radioactivity in stool. A similar effect was observed in intact animals. We conclude that chlordecone enters the intestinal lumen from a nonbiliary source, probably the gut, and that net excretion of chlordecone from this source can be augmented by cholestyramine.