Takeo S, Miyake K, Minematsu R, Tanonaka K, Konishi M
Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuyama University, Japan.
J Pharmacol Exp Ther. 1989 Mar;248(3):1207-14.
The present study was designed to determine whether naftidrofuryl oxalate (Naftidrofuryl) may exert a beneficial effect on the cerebral mitochondria after microsphere-induced embolism assessed under in vitro conditions. For this purpose, 600 microspheres (48 microns in diameter) were injected into the right carotid canal of rats, which induced an irreversible embolism in the right cerebrum. Three days after the operation, the cerebral mitochondria were isolated and their oxidative phosphorylation ability and succinate dehydrogenase activity were determined. Two types of mitochondria were obtained after cerebral embolism: one was mitochondria which revealed a marked decline in the oxidative phosphorylation activity when measured in the presence of glutamate or succinate as a substrate (severely injured mitochondria), and the other, those which revealed a decrease in the activity in the presence of succinate and an appreciable increase in the activity in the presence of glutamate (mildly injured mitochondria). Naftidrofuryl at the concentration of 3 microM elicited slight but significant restoration of the oxidative phosphorylation ability of the mildly injured mitochondria isolated from rats after the cerebral embolism, but not of the severely injured mitochondria. The succinate dehydrogenase activity of the brain mitochondria isolated from rats 3 days after the cerebral embolism was significantly decreased. Exposure of these mitochondria to 0.1 to 1 microM Naftidrofuryl significantly restored the succinate dehydrogenase activity. The results suggest that Naftidrofuryl is capable of exerting a beneficial effect in vitro on the brain mitochondria activity impaired by the cerebral embolism, particularly on the activity of mildly injured mitochondria.
