THE EFFECT OF QUINAZOLINONE DERIVATIVES ON MITOCHONDRIAL FUNCTION OF BRAIN CELLS IN RATS WITH FOCAL CEREBRAL ISCHEMIA

Abstract

The studied quinazolinone derivatives at doses of 40 mg/kg and the reference drug ethylmethylhydroxypyridine succinate at a dose of 100 mg/kg were administered orally to rats for 3 days from the onset of ischemia modeling. It was found that under conditions of focal cerebral ischemia in rats, the activity of citrate synthase, cytochrome c-oxidase and succinate dehydrogenase decreased in the mitochondrial fraction of brain tissue by 73, 67 and 49% (p < 0.05), respectively, and was accompanied by an increase in the concentration of mitochondrial hydrogen peroxide by 2.8 times and apoptosis-inducing factor by 7.1 times (p < 0.05), with inhibition of aerobic and activation of anaerobic respiration by 31% (p < 0.05) and 4.3 times (p < 0.05), respectively. The use of ethylmethylhydroxypyridine succinate resulted in an increase in the activity of mitochondrial enzymes by an average of 59% (p < 0.05), decreased the content of mitochondrial hydrogen peroxide and apoptosis-inducing factor by 40 and 26% (p < 0.05), increased aerobic respiration by 34% (p < 0.05) and decreased anaerobic respiration by 50% (p < 0.05). Substances marked as RP-4 and RP-5 (2-[[2-(2-isopropyl-6,7-dimethoxy-4-oxoquinazoline-3-yl)acetyl]amino]acetic acid and 2-[[2-(2-propyl-6,7-dimethoxy-4-oxo-quinazoline-3-yl)acetyl]amino]acetic acid, respectively) in the mitochondrial fraction of brain tissue increased the activity of mitochondrial enzymes, aerobic metabolism by 23.9 and 30.3% (p < 0.05) with a decrease in anaerobic by 32.4 and 24.5% (p < 0.05), reduced the concentration of mitochondrial hydrogen peroxide by 20.7 and 19.5% (p < 0.05) and apoptosis-inducing factor in the brain tissue supernatant by 23.4 and 21.1% (p < 0.05).