Geroprotective effects of ethylmethylhydroxypyridine succinate in an experimental study


FSBI «Zakusov Institute of Pharmacology», Moscow

Objective. To study an effect of mexidol on the life expectancy, weight, seizure response thresholds, and impaired cognitive and
motor functions during aging in male Wistar rats. Material and methods. In a long-term experiment, male Wistar rats, aged 3—26 months, were assessed for impaired cognitive functions (passive avoidance conditioned reflex test), convulsive threshold (test with pentylenetetrazole), motor deficits (tests of rotating rod and pulling on the crossbar), and life expectancy. The rats received mexidol in the form of 0,15% solution, which replaced drinking water, during two 2 month courses at the age of 18—20 and 22—24 month. A dose of mexidol consumed by the rat was 40-75 mg/kg/day. Results. In old male Wistar rats, the long-term treatment with mexidol increases the life expectancy, improves learning, preservation and reproduction of the memory trace in the passive avoidance conditioned reflex test, increases the convulsive threshold and improves muscle tone and coordination of movements that are impaired during aging. Conclusion. Mexidol increases the threshold of convulsive reaction, restores cognitive and neurological deficits that occur during aging in male Wistar rats and increases the by its ability to influence mitochondriogenesis and antioxidant properties.
Keywords: aging, mexidol, life expectancy, memory impairment, neurological deficit, convulsive threshold.

The effect of Mexidol on cerebral mitochondriogenesis at a young age and during aging


1 Institute of General Pathology and Pathophysiology, Moscow, Russia;

2 Zakusov Research Institute of Pharmacology, Moscow, Russia

Objective. To study the ability of mexidol to induce cerebral mitochondriogenesis in the brain of young and aging rats. Material and methods. Expression level of marker proteins of cerebral mitochondriogenesis was evaluated during treatment with mexidol (20, 40, 100 mg/kg; 20 days; intraperitoneally) in the cerebral cortex of young (3 month) and aging (6, 9, 12, and 15 month) outbred male rats, using the Western blot analysis. Results. It has been shown for the first time that the course injections of mexidol in doses of 40 and 100 mg/kg is accompanied by dose-dependent induction of the succinate receptor SUCNR1 and protein markers of mitochondrial biogenesis: transcription coactivator PGC-1α, transcription factors (NRF1, TFAM), catalytic subunits of respiratory enzymes (NDUV2, NDUV2,cytb, COX2) and ATP synthase (ATP5A) in the cerebral cortex of young and aging outbred male rats. Mexidol-dependent overexpression of subunits of mitochondrial enzymes and PGC-1α is observed only with the course of the drug. Conclusion. The results indicate the ability of mexidol to induce cerebral mitochondriogenesis and eliminate mitochondrial dysfunction in young and aging animals and, thus, exert an effect on one of the key pathogenetic links of the development of disorders in aging and neurodegenerative diseases.
Keywords: aging, mitochondrial dysfunction, mexidol, succinate receptor, cerebral mitochondriogenesis, transcriptional coactivator PGC-1α, respiratory enzyme subunits, rats, Western blot analysis.