Inhibitory effect of beraprost sodium on formation of lipid peroxides in ischemia and recirculation-induced cerebral injury.
A cerebral injury was induced by the bilateral common carotid artery occlusion and recirculation in spontaneously hypertensive rats (SHRs). Employing this ischemia-recirculation rat model, the effects of beraprost sodium (beraprost) on (1) lipid peroxide formation, (2) the increase in the brain water content and (3) neurological signs were examined. In a dosage of 25 micrograms kg-1 or higher, beraprost, administered orally, significantly inhibited the formation of lipid peroxides in the brain and serum induced by cerebral ischemia and subsequent recirculation in a dose-dependent manner. Beraprost also alleviated ptosis and markedly inhibited abnormal running behaviour caused by the ischemia and subsequent recirculation. In addition, although administration of beraprost did not cause marked inhibition of the increase in the brain water content (used as an index of cerebral oedema) during the first 3 h after recirculation, it restored the normal brain water content within 24 h after recirculation. Therefore, this effect was observed evidently later than the effect of inhibition of lipid peroxide formation. Moreover, administration of beraprost resulted in improvement in the symptoms accompanying the ischemic treatment. These results suggest that beraprost is potentially useful for or treatment of the pathological state accompanying cerebral infarction.
Kainoh
M
M
Laboratory of Pharmacology, Toray Industries, Inc., Kanagawa, Japan.
Ueno
S
S
Endoh
T
T
Nakadate
T
T
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001834:Body Water / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D002545:Brain Ischemia / Q000378:metabolism* / Q000517:prevention & control; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008054:Lipid Peroxides / Q000097:blood / Q000378:metabolism*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D015427:Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control
D008054:Lipid Peroxides; C048081:beraprost; D011464:Epoprostenol