The effects of idebenone on DNA and RNA contents as well as synthesis rates of total and poly(A)+ RNA in brain of normal, old C57BL/6J mice and in experimental partial cerebral ischemia of rats.
Effects of idebenone on RNA and DNA contents as well as on synthesis rates of total and poly(A)(+) RNA in the brain were measured in two animal models: (1) Normal young and old, male C57BL/6J mice (6 and 32 months). Idebenone suspended in 5% gum arabic was applied in 50 mg/kg/day dose to old mice for 1 month through a gastric tube. (2) Adult female CFY rats (14-18 months) in which experimental partial cerebral ischemia was induced by bilateral common carotid artery occlusion. Idebenone was administered intraperitoneally in two dose (10mg/kg and 100 mg/kg body weight) 30 min before the interruption of carotid blood flow. DNA content remained invariate during aging in the brain; idebenone treatment did not exert any influence on this parameter. RNA content as well as total and poly(A)(+) RNA synthesis rates, which were measured by incorporation of tritiated uridine into RNA, decreased significantly with age in brain. Idebenone treatment did not cause any essential change of the metabolism of RNA under the given conditions. The RNA and DNA contents of brain were influenced neither by experimental partial cerebral ischemia nor by treatment with idebenone during the ischemia. Partial cerebral ischemia decreased the rate of total and poly(A)(+) RNA synthesis in the brain about 15-45% depending on the methods and basis of expression. This decline could totally be prevented by intraperitoneal application of 10 mg/kg idebenone 30 min before the onset of the partial ischemia. The dose of 100 mg/kg idebenone also elevated the rate of RNA synthesis; however, this increase remained statistically insignificant.
Semsei
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NIII-NIA, Gerontological Research Center, Francis Scott Key Medical Center, Baltimore, MD 21224, USA.
Cutler
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Zs -Nagy
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