title: Effects of chlordecone and its alteration products on isolated rat liver mitochondria.
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.
mesh_terms: 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
chemical_list: D007306:Insecticides; D009243:NAD; C029713:chlordecone alcohol; D014634:Valinomycin; C024579:monohydrokepone; C024580:dihydrokepone; D007631:Chlordecone