Metabolic effects of 3-substituted chromone derivatives in experimental chronic traumatic encephalopathy

Abstract

Aim to evaluate the effect of five new 3-substituted chromone derivatives on changes in mitochondrial function and the development of tau pathology in animals under experimental chronic traumatic encephalopathy. Material and methods. Chronic traumatic encephalopathy was modeled in Wistar rats by repeated exposure to a shock wave (2 atm.) on the animal's head for seven days. The studied compounds (X3A1 X3A5) and the reference citicoline were administered 60 minutes after injury at doses of 40 mg/kg and 150 mg/kg orally. On the eighth day of the experiment, changes in the mass coefficient of the brain, the concentration of phosphorylated tau protein in brain tissue and changes in the activity of cytochrome-c-oxidase and succinate dehyrogenase were evaluated in animals. Results. The use of compounds X3A4 and X3A5 equally to citicoline reduced the development of tau pathology, increased the activity of mitochondrial enzymes: cytochrome-c-oxidase by 14.5% (p0.05), 41.9% (p0.05) and 22.6% (p0.05), respectively; succinate dehydrogenase by 28.6% (p0.05); 33.2% (p0.05) and 22.8% (p0.05), respectively. As a result, against the background of the administration of these compounds, an increase in brain mass coefficient was noted in relation to the animals that did not receive a pharmacological support. Conclusion. Administration of chromone derivatives X3A4 and X3A5 to animals with experimental chronic traumatic encephalopathy prevents the development of tau pathology and atrophy of brain tissue, probably due to metabolic action, expressed in the restoration of mitochondrial function.