INFLUENCE OF A CINNAMIC ACID DERIVATIVE ON CHANGES IN THE ACTIVITY OF MITOCHONDRIAL RESPIRATORY CHAIN COMPLEXES IN EXPERIMENTAL BRAIN ISCHEMIA

DOI: https://doi.org/10.29296/25877313-2020-06-09
Issue: 
6
Year: 
2020

D.I. Pozdnyakov Ph.D. (Pharm.), Head of Living System Laboratory, Associate Professor, Department of Pharmacology with Clinical Pharmacology Course, Pyatigorsk Medical and Pharmaceutical Institute E-mail: pozdniackow.dmitry@yandex.ru D.S. Zolotyh Ph.D. (Pharm.), Associate Professor, Analytical Chemistry Department, Pyatigorsk Medical and Pharmaceutical Institute E-mail: metranidazol@mail.ru M.V. Larskij Ph.D. (Pharm.), Head of Pharmaceutical Chemistry Department, Pyatigorsk Medical and Pharmaceutical Institute E-mail: pharmachemistry@mail.ru

Relevance. It is known that mitochondrial dysfunction is a significant pathogenetic mechanism of ischemic brain damage and a promising pharma-cotherapeutic target for cerebroprotective therapy. The aim of the study. To evaluate the effect of 4-hydroxy-3,5-di-tret-butyl cinnamic acid on the change of the mitochondrial respiratory chain com-plexes activity in rats brain supernatant in cerebral ischemia conditions. Material and methods. The study was performed on male Wistar rats that reproduced cerebral ischemia using the Tamura method. 4-hydroxy-3,5-di-tret-butyl cinnamic acid was administered at a dose of 100 mg / kg (per os) after 30 minutes when ischemia was reproduced and then once a day for 3 days. On day 4, a change in the activity of mitochondrial complexes I, II, IV, and V in the supernatant of the brain was assessed by the respiro-metric method. Results. Against the background of the administration of 4-hydroxy-3,5-di-tret-butyl cinnamic acid into animals, an increase in the activity of mito-chondrial complexes was noted: NADH-dehydrogenase; succinate dehydrogenase; cytochrome c - oxidase; F1F0 ATP synthase in relation to animals that did not receive pharmacological support by 71% (p < 0.05); 86% (p < 0.05); 2.29 times (p < 0.05) and 1.9 times (p < 0.05) times, respectively. It should be noted that the 4-hydroxy-3,5-di-tret-butyl cinnamic acid test compound exceeded the reference drug succinic acid in an equivalent dose in terms of therapeutic efficacy. Conclusions. Based on the obtained results it can be assumed that 4-hydroxy-3,5-di-tret-butyl cinnamic acid has a cerebroprotective effect due to the restoration of mitochondrial function and the elimination of energy deficiency arising in the area of ischemic penumbra.

Keywords: 
cerebral ischemia
mitochondrial dysfunction
cinnamic acid derivatives

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