title: Effects of naftidrofuryl oxalate on microsphere embolism-induced changes in tricarboxylic acid cycle intermediates of rats.
abstract: The present study was undertaken to determine whether naftidrofuryl oxalate, a cerebral vasodilator, may improve or attenuate microsphere embolism-induced damage to the mitochondrial tricarboxylic acid cycle. For this purpose, the intermediates in the tricarboxylic acid cycle were determined using cerebral cortex isolated from microsphere-injected rats with and without naftidrofuryl oxalate treatment. Seven-hundred microspheres, with a diameter of 48 microns were injected into the right hemisphere through the right common carotid artery. The presence of cerebral infarction on the 3rd day after the operation was confirmed by the development of triphenyltetrazolium chloride-unstained areas in brain sections. Succinate, fumarate, malate, citrate and alpha-ketoglutarate, but not oxaloacetate, contents were significantly decreased in the right hemisphere of rats on the 3rd day following microsphere embolism. In the left hemisphere, a similar but smaller decrease in these intermediates was seen. The rats, which showed typical stroke-like symptoms, were treated with 15 mg/kg naftidrofuryl oxalate i.p., twice daily for 2.5 days, resulting in a significant reversal of the intermediate content of both hemispheres toward the control and an increased in the triphenyltetrazolium-stained area of a coronal section of the right hemisphere relative to the untreated animals. The results suggest that naftidrofuryl oxalate attenuates the development of microsphere embolism-induced cerebral infarction and improves microsphere-induced impairment of the mitochondrial tricarboxylic acid cycle. The observed effects provided evidence for a possible site of action of the agent on ischemic brain energy metabolism.
authors.affiliation: Department of Pharmacology, Tokyo College of Pharmacy, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Miyake
authors.forename: K
authors.initials: K
authors.lastname: Tanonaka
authors.forename: Y
authors.initials: Y
authors.lastname: Nasa
authors.forename: N
authors.initials: N
authors.lastname: Takagi
authors.forename: T
authors.initials: T
authors.lastname: Tsuchiya
authors.forename: M
authors.initials: M
authors.lastname: Yoshizawa
authors.forename: Y
authors.initials: Y
authors.lastname: Fujioka
authors.forename: S
authors.initials: S
authors.lastname: Takeo
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D002951:Citrates / Q000378:metabolism; D019343:Citric Acid; D002952:Citric Acid Cycle / Q000187:drug effects*; D005650:Fumarates / Q000378:metabolism; D002542:Intracranial Embolism and Thrombosis / Q000378:metabolism*; D007656:Ketoglutaric Acids / Q000378:metabolism; D008293:Malates / Q000378:metabolism; D008297:Male; D008863:Microspheres; D009257:Nafronyl / Q000494:pharmacology*; D010071:Oxaloacetates / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling; D013386:Succinates / Q000378:metabolism; D019802:Succinic Acid; D013778:Tetrazolium Salts
chemical_list: D002951:Citrates; D005650:Fumarates; D007656:Ketoglutaric Acids; D008293:Malates; D010071:Oxaloacetates; D013386:Succinates; D013778:Tetrazolium Salts; D019343:Citric Acid; D009257:Nafronyl; C009591:triphenyltetrazolium; C032005:fumaric acid; D019802:Succinic Acid