Effects of idebenone on the levels of acetylcholine, choline, free fatty acids, and energy metabolites in the brains of rats with cerebral ischemia.
Cerebral ischemia was induced by a 200-s occlusion of both common carotid arteries in rats in which both vertebral arteries had been permanently cauterized. In the ischemic rats, a significant decrease in acetylcholine (ACh) and a marked increase in choline were observed in the cerebral cortex, hippocampus, striatum, and diencephalon. A slight increase in choline was also observed in the cerebellum and brain stem. Pretreatment with idebenone (10 mg/kg, i.p.) inhibited the decrease in ACh and the increase in choline in the forebrain regions. In addition, the same dose of idebenone inhibited the increments of lactate and free fatty acid contents and tended to inhibit the decrement of the ATP content in the cerebral cortex of the cerebral ischemic rats. These results indicate that idebenone inhibits the alteration of the ACh level and the disruption of membrane phospholipids in the brain of ischemic rats; these effects may be mediated by improved cerebral energy metabolism.
Kakihana
M
M
Central Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
Yamazaki
N
N
Nagaoka
A
A
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D016227:Benzoquinones; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism*; D002794:Choline / Q000378:metabolism*; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D008297:Male; D011809:Quinones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014451:Ubiquinone / Q000031:analogs & derivatives
D016227:Benzoquinones; D005230:Fatty Acids, Nonesterified; D011809:Quinones; D014451:Ubiquinone; C036619:idebenone; D002794:Choline; D000109:Acetylcholine