Cardioprotector Angiolin with original structure 3-methyl-1,2,4-triazolyl-5-thioacetate (S)-2,6-diaminohexanoic acid and its dosage form 2,5% solution for injection were developed by Scientific and Production Corporation "Pharmatron". Angiolin administration in dose of 50 mg/kg to the animals with pituitrin-isadrin myocardial infarction resulted in normalization of energy metabolism of the heart due to intensification of aerobic reactions and compensatory activation of malate-aspartate shuttle, in decrease of anaerobic glycolysis and improvement of mitochondria functions, saving use of oxidation substrates and activation of energy transport. Thus, in myocardium of the animals with myocardial infarction which received Angiolin the increase of ATP production was noted against the background of the increase of levels of such malate-aspartate shuttle components as malate, aspartate, glutamate and malate dehydrogenase activation as well as isocitrate content growth and lactate level decrease as compared with untreated animals group. Increase of glycogen and glucose 6-phosphate contents, increase of mitochondrial and cytosolic creatine phosphokinase activity took place in animals' myocardium when administrating Angiolin. Thus Angiolin administration at myocardial infarction forms resistance of cardiac hystiocytes to hypoxia due to energy pathways change which supposes mobilization of mechanisms of protons supply for oxidative phosphorylation and saving use of deficient oxygen. Angiolin therapeutical efficiency significantly exceeds the efficiency of reference drug Mildronate (100 mg/kg).
В монографии представлена современная концепция молекулярнобиохимических механизмов гибели нейронов в условиях острой церебральной ишемии.Показана роль глутамат-кальциевого каскада (изменения метаболизма глутамата и кальция, оксидативный стресс, гиперпродукция NO ), митохондриальной дисфункции, дискоординации тиол-дисульфидной системы, которые индуцируют отдаленные последствия ишемии -реакцию генома с включением генетически запрограммированных молекулярных механизмов, дисфункцию астроцитарного и микроглиального пулов, развитие иммунных изменений и инициацию нейроапоптоза.Представлены данные о значении молекулярных факторов эндогенной нейропротекции.Выделены два основных направления терапии мозгового инсультапервичная нейропротекция, направленная на прерывание быстрых механизмов некротической смерти клеток и вторичная нейропротекция, цель которой -уменьшение выраженности отдаленных последствий ишемии (блокада провоспалительных цитокинов, молекул клеточной адгезии, торможение оксидативного стресса, нормализация нейрометаболических процессов, ингибирование апоптоза
Chronic (15 days) single daily intraperitoneal insertion of the new preparation MT (5 mg/kg) and metoprolol (10 mg/kg) into SHR rats leads to the same decrease (18%) in arterial pressure. In addition, MT exhibits a cardioprotective effect because of NO-mimetic properties, increasing NO formation in myocardium via increasing general NOS activity and eNOS expression. MT normalizes iNOS expression in myocardium mitochondria and decreases nitrotyrosine (nitrosation stress marker) formation. At the same time, the reference preparation metoprolol did not exhibit NO-mimetic properties in myocardium of SHR rats.
