title: Models for clinical disease. I. Biochemical cardiotoxicity of a coenzyme Q10-inhibitor in rats.
abstract: The pharmacology and toxicity in animals of synthetic analogs of essential metabolites, which show in vitro antagonism of the metabolite, may point out pathology associated with a deficiency of the metabolite. On this basis, 2-hydroxy-3-n-dodecylmercapto-1,4-naphthoquinone, a potent in vitro inhibitor of a mitochondrial coenzyme Q10-enzyme, was administered to rats. The specific activities and the percent deficiencies of the succinate dehydrogenase-coenzyme Q10 reductase in cardiac mitochondria were significantly increased (0.001 less than P less than 0.01). These enzyme activities were unchanged in leucocytes and in the dorsal aorta. This biochemical cardiotoxicity of an antimetabolite of coenzyme Q10 adds to the advancing knowledge on coenzyme Q10 in cardiac metabolism and disease, and could correlate with the cardiotoxicity of the clinical antitumor drug, adriamycin.
mesh_terms: D000818:Animals; D001011:Aorta / Q000648:ultrastructure; D066298:In Vitro Techniques; D007962:Leukocytes / Q000648:ultrastructure; D008928:Mitochondria / Q000187:drug effects; D009206:Myocardium / Q000648:ultrastructure; D009285:Naphthoquinones / Q000494:pharmacology*; D051381:Rats; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013440:Sulfides / Q000494:pharmacology; D014451:Ubiquinone / Q000037:antagonists & inhibitors*
chemical_list: D009285:Naphthoquinones; D013440:Sulfides; D014451:Ubiquinone; C011855:2-hydroxy-3-n-dodecylmercapto-1,4-naphthoquinone; D013385:Succinate Dehydrogenase