New evaluation of potential methylmercury scavengers.
A biological assay was developed to evaluate rapidly the relative efficacy of marketed and experimental mercurial scavengers. Rat liver mitochondrial protein (1.0 mg) was titrated against methyl-mercuric chloride to the inhibitory level of mitochondrial respiration. Respiration induced by adenosine 5'-diphosphate with succinate (plus rotenone) as the substrate was inhibited consistently by 20.7 +/- 3.9 nmoles of methylmercury/mg of protein. Adenosine 5'-diphosphate-stimulated respiration (State 3) was restored with dimercaprol, penicillamine, and cysteine but not with serine. The antagonists glutathione, 3-mercapto-propionic acid, 2-mercaptoethanol, dithiothreitol, thioglucose, mercaptosuccinic acid, and thiosalicylic acid and mercaptosuccinic acid. Sodium sulfide, thioacetamide, and ethylenediaminetetraacetic acid were completely inactive. Substitution of glutamate (plus malate) for succinate (plus rotenone) as the substrate did not alter the responses significantly. The rat liver mitochondrial assay provides preliminary information about the efficacy and toxicity of water-soluble thiols. Investigations utilizing encapsulated water- and lipid-soluble mercaptans are in progress.
D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D066298:In Vitro Techniques; D008767:Methylmercury Compounds / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats
D002614:Chelating Agents; D008767:Methylmercury Compounds