Stimulation of the respiratory and phosphorylating activities in rat brain mitochondria by idebenone (CV-2619), a new agent improving cerebral metabolism.
The effects of 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (CV-2619) on the respiration and non-respiratory oxygen consumption induced by ascorbate and Fe2+ in rat brain mitochondria were studied. When CV-2619 (100 and 300 mg/kg) was orally administered to rats for 3 days, it increased the state 3 respiration stimulated by ADP, slightly decreased the state 4 respiration after the consumption of ADP and resulted in a significant increase of the respiratory control index (RCI) by 14-19% for glutamate oxidation (p less than 0.01) and 10-17% for succinate oxidation (p less than 0.05), respectively. The RCI increasing effect of CV-2619 was dose dependent, but the compound had no effect on the ADP/O ratio. CV-2619 significantly suppressed by about 10% the non-respiratory oxygen consumption (p less than 0.02), which closely associated with non-enzymatic reactions such as lipid peroxidation, membrane lysis and swelling of mitochondria. Thus, CV-2619 may contribute to stimulate the net ATP formation by the well-coupling of electron and energy transfer, and by the reduction of non-respiratory oxygen consumption in cerebral metabolism.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D016227:Benzoquinones; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D010766:Phosphorylation; D011809:Quinones / Q000494:pharmacology*; D051381:Rats; D014451:Ubiquinone / Q000031:analogs & derivatives
D016227:Benzoquinones; D011809:Quinones; D014451:Ubiquinone; D000244:Adenosine Diphosphate; C036619:idebenone