Pozdnyakov D I, Zolotykh D S, Vihor A A
Pyatigorsk Medical and Pharmaceutical Institute - Branch of the Volgograd State Medical University, Pyatigorsk, Russia.
Zh Nevrol Psikhiatr Im S S Korsakova. 2023;123(11):111-116. doi: 10.17116/jnevro2023123111111.
To evaluate an effect of ethylmethylhydroxypyridine succinate and ethylmethylhydroxypyridine malate on changes in mitochondrial function under experimental focal cerebral ischemia.
Focal cerebral ischemia was modeled in rats by thermocoagulation of the middle cerebral artery. Ethylmethylhydroxypyridine succinate («Mexidol») and ethylmethylhydroxypyridine malate («Ethoxidol») were injected into the tail vein 30 minutes after ischemia simulation and then for 3 days at doses of 50 mg/kg, 100 mg/kg and 150 mg/kg. After 72 hours, changes in neurological deficits, aerobic and anaerobic respiration activity, the concentration of mitochondrial hydrogen peroxide and apoptosis-inducing factor, as well as the activity of succinate dehydrogenase and cytochrome c oxidase in brain tissue supernatants were assessed.
The course administration of ethylmethylhydroxypyridine succinate and ethylmethylhydroxypyridine malate dose-dependently contributed to a decrease in the concentration of mitochondrial hydrogen peroxide and apoptosis-inducing factor in the brain tissue. The restoration of mitochondrial energy function was also shown with the use of ethylmethylhydroxypyridine succinate in all studied doses, while the administration of ethylmethylhydroxypyridine malate led to the restoration of mitochondrial-dependent energy production only at higher doses (100 mg/kg and 150 mg/kg).
The effect of malic acid and succinic acid salts of ethylmethylhydroxypyridine on the change in the redox and apoptosis-regulating function of mitochondria does not depend on the type of anion, whereas the change in the energy function of mitochondria is associated with the salt residue included in the drug structure and its dosage.
评估琥珀酸乙甲基羟基吡啶和苹果酸乙甲基羟基吡啶对实验性局灶性脑缺血后线粒体功能变化的影响。
通过热凝大脑中动脉在大鼠中建立局灶性脑缺血模型。在缺血模拟后30分钟，将琥珀酸乙甲基羟基吡啶（“美西多芬”）和苹果酸乙甲基羟基吡啶（“乙氧多醇”）经尾静脉注射，然后以50mg/kg、100mg/kg和150mg/kg的剂量连续注射3天。72小时后，评估神经功能缺损、有氧和无氧呼吸活性、线粒体过氧化氢和凋亡诱导因子的浓度，以及脑组织上清液中琥珀酸脱氢酶和细胞色素c氧化酶的活性变化。
琥珀酸乙甲基羟基吡啶和苹果酸乙甲基羟基吡啶的疗程给药剂量依赖性地导致脑组织中线粒体过氧化氢和凋亡诱导因子浓度降低。在所有研究剂量下，使用琥珀酸乙甲基羟基吡啶均显示出线粒体能量功能的恢复，而仅在较高剂量（100mg/kg和150mg/kg）下，苹果酸乙甲基羟基吡啶的给药才导致线粒体依赖性能量产生的恢复。
乙甲基羟基吡啶的苹果酸盐和琥珀酸盐对线粒体氧化还原和凋亡调节功能变化的影响不取决于阴离子类型，而线粒体能量功能的变化与药物结构中所含的盐残基及其剂量有关。
