Stimulation of the respiratory and phosphorylating activities in rat brain mitochondria by idebenone (CV-2619), a new agent improving cerebral metabolism

Abstract

AbstractThe effects of 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-l,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 mgkg) 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<0.01) and 10–17% for succinate oxidation (P<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<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