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Title: Effects of chlordecone and its alteration products on isolated rat liver mitochondria.

Authors: Soileau, S D; Moreland, D E

Published In Toxicol Appl Pharmacol, (1983 Jan)

Abstract: Partitioning of chlordecone, chlordecone alcohol, monohydrochlordecone, and dihydrochlordecone (2 to 100 microM) into isolated rat liver mitochondria altered the permeability properties of the inner membrane as evidenced by: inhibition of valinomycin-induced swelling, induction of passive swelling, oxidation of exogenous NADH, and induction of lysis. Associated with the increase in permeability were stimulation of state 4 and inhibition of state 3 respiration for the oxidation of both succinate and glutamate. Except for the inhibition of valinomycin-induced swelling, the following order of potency for all assays was obtained: chlordecone alcohol greater than or equal to chlordecone greater than monohydrochlordecone much greater than dihydrochlordecone. Mirex, a 12-chlorine analog of chlordecone, and a dioxolane-chlordecone adduct did not affect any of the reactions at saturating concentrations of 40 and 100 microM, respectively. The hydrated ketone, or a hydroxyl moiety, and a high chlorine content appear to be responsible for lytic and inhibitory activity. Lysis resulted in the leakage of water-soluble matrix enzymes from the mitochondria, but not in the solubilization of integral proteins.

PubMed ID: 6189267 Exiting the NIEHS site

MeSH Terms: Animals; Chlordecone/analogs & derivatives; Chlordecone/toxicity*; Dose-Response Relationship, Drug; In Vitro Techniques; Insecticides/toxicity*; Male; Mitochondria, Liver/drug effects*; Mitochondria, Liver/metabolism; NAD/metabolism; Oxygen Consumption/drug effects; Rats; Rats, Inbred Strains; Structure-Activity Relationship; Valinomycin/pharmacology

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