[Cerebroprotective action of naftidrofuryl oxalate. I: Prolongation of survival time and protection of cerebral energy metabolism in bilateral carotid artery-ligated mice].
The present study was designed to elucidate whether naftidrofuryl oxalate (LS-121) may exert a beneficial effect on survival time and cerebral energy metabolism of bilateral carotid artery (BCA)-ligated mice. Survival time of BCA-ligated mice ranged from 100 to 308 sec. Administration of 15, 45 and 100 mg/kg, i.p. and 100 mg/kg, p.o. LS-121 significantly prolonged the survival time. Cerebral adenosine triphosphate (ATP), creatine phosphate (CP) and glucose contents were markedly reduced at 2 min after BCA-ligation. Cerebral lactate content was increased by the ligation, whereas the pyruvate content was not altered. Pretreatment of mice with 15, 45 mg/kg, i.p. and 100 mg/kg, p.o. LS-121 suppressed BCA-ligation induced decrease in high-energy phosphates of the mouse brain. Ligation-induced decrease in glucose and increase in lactate content tended to be attenuated by the treatment with 45 mg/kg, i.p. LS-121. Time course of changes in metabolic variables altered by BCA-ligation with and without the pretreatment with 45 mg/kg, i.p. LS-121 showed a significant suppression of ligation-induced decrease in cerebral high-energy phosphates. The results suggest that LS-121 is beneficial for ischemic mouse brain energy metabolism, which may be related to the prolongation of the survival time.
Takeo
S
S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Fukuyama University, Japan.
Tanonaka
K
K
Hirano
T
T
Miyake
K
K
Okamoto
J
J
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D002339:Carotid Arteries; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005663:Furans / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009257:Nafronyl / Q000494:pharmacology / Q000627:therapeutic use*
D005663:Furans; D009257:Nafronyl