Federal State Budgetary Institution «Research Institute of Pharmacology», Siberian Branch of the RAMS, Tomsk, Russian Federation
*Corresponding author: Roman V. Gurto, PhD, Leading Researcher, Laboratory of Physiology, Molecular and Clinical Pharmacology, Federal State Budgetary Institution «Research Institute of Pharmacology», Siberian Branch of the Russian Academy of Medical Sciences, 3, Lenin ave., 634028, Tomsk, Russian Federation. Tel/Fax: 7-3822-418373 E-Mail:firstname.lastname@example.org
The present paper demonstrates the effect of acetylsalicylic acid (ASA) and its combination with succinic acid (SUC) on the energy-producing system of rat heart mitochondria as well as an assessment of SUC preventive application effect on ASA pharmacokinetic parameters. Experiments conducted on outbred male albino rats (200-250 g) on a model of a xenobiotic load induced by seven days of intragastric injections of acetylsalicylic acid at a dose of 250 mg/kg have shown inhibition of the oxygen consumption rates in the heart mitochondria as well as a limitation of the succinate-dependent substrate oxidation pathways and a decrease in the mitochondria ATP/ADP coefficient. Succinic acid (50 mg/kg for 7 days) was injected as a preventive medication to correct the mitochondrial bioenergetics revealed. A comparative research of the pharmacokinetics of acetylsalicylic acid and acetylsalicylic acid against the background of succinic acid performed on the model of rabbits has shown total similarity in the parameters analyzed. This fact demonstrates the possibility of prevention of mitochondrial dysfunction using the intermediate Krebs cycle. SUC as preventive medication promotes the elimination of ASA-induced negative metabolic shifts in the rat heart mitochondria by normalizing the succinate- and NAD-dependent respiration, oxidative phosphorylation, and therefore, it finds good use in the correction of ASA-induced negative side-effects of an energy-generating system.
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