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[Molecular mechanisms of hypoxia and adaptation to it. Part II].
Arkh Patol
May 2021
St. Petersburg State Chemical Pharmaceutical University, St. Petersburg, Russia.
Reprogramming of the mitochondrial electron transport chain (ETC) is the most important physiological mechanism that provides short- and long-term adaptation to hypoxia. The possibilities of additional pharmacological regulation of ETC activity are of considerable practical interest in correcting hypoxia-associated disorders. This review considers the main groups of antihypoxic compounds that exhibit their effect at the interface of ETC and the cycle of tricarboxylic acids, including succinate-containing and succinate-forming antihypoxants.
View Article and Find Full Text PDFExperiments with mice showed that, unlike reamberin (100 mg/kg), mexidol (100 mg/kg) and cytoflavin (1 ml/kg) act as antihypoxants in pressure and hermetic chambers but not in case of acute hemic and histotoxic hypoxia. Amtisol succinate (100 mg/kg), a reference antihypoxant, excels the other tried succinate-containing drugs in all models of acute hypoxia except the hermetic chamber. In addition, the neuroprotective action of mexidol (100 mg/kg/d) and cytoflavin (100 ml/kg/d) in rats with induced ischemic stroke which was stronger than that of reamberin and amtisol succinate (100 mg/kg/d).
View Article and Find Full Text PDFHypoxia is a universal process accompanying and determining the development of various pathological conditions. In the most general form hypoxia can be defined as the incompatibility between energy requirements of the cell and energy production in the system of mitochondrial oxidative phosphorylation. The energetic status of the cell can be improved by such pharmacological products as antihypoxants of 5 groups: inhibitors of fatty acid oxidation, succinate-containing and succinate-producing agents, components of the natural respiratory chain, artificial redox-systems, and macroergic compounds.
View Article and Find Full Text PDFExperiments with mice demonstrated that in contrast to the preparations for comparison (mexidol and reference antihypoxant succinate amtisol at a dose of 1-100 mg/kg) new succinate-containing derivatives of benzothiazole BTI-2 (0.5-5 mg/kg), BTI-3 (0.1, 0.
View Article and Find Full Text PDFAntihypoxic and antioxidant effects of exogenous succinic acid and aminothiol succinate-containing antihypoxants.
Bull Exp Biol Med
July 2012
Department of Pharmacology, SM Kirov Military Medical Academy, St. Petersburg, Russia.
Pronounced antihypoxic and antioxidant effects of preventive injection of succinic acid, aminothiol antihypoxants gutimine and amtizol, and succinate-containing aminothiol antihypoxants gutimine succinate and amtizol succinate to Wistar rats with acute hypoxic hypoxia have been demonstrated. Exogenous succinic acid was inferior to aminothiol compounds by antihypoxic effect, but superior to them by its effect on the level of LPO products. Succinate in the aminothiol molecule modulated the intensity of their antihypoxic and antioxidant effects.
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