Effects of chlordecone and its alteration products on isolated rat liver mitochondria.
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.
D000818:Animals; D007631:Chlordecone / Q000031:analogs & derivatives / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D014634:Valinomycin / Q000494:pharmacology
D007306:Insecticides; D009243:NAD; C029713:chlordecone alcohol; D014634:Valinomycin; C024579:monohydrokepone; C024580:dihydrokepone; D007631:Chlordecone