The Administration of the New Pyrimidine Derivative-4-{2-[2-(3,4-Dimethoxyphenyl)-Vinyl]-6-Ethyl-4-Oxo-5-Phenyl-4H-Pyrimidine-1-Il}Benzsulfamide Restores the Activity of Brain Cells in Experimental Chronic Traumatic Encephalopathy by Maintaining Mitochondrial Function

Medicina (Kaunas). 2019 Jul 17;55(7):386. doi: 10.3390/medicina55070386.

Abstract

Background and objectives: To evaluate the effect of a new pyrimidine derivative on the change of mitochondrial function in experimental chronic traumatic encephalopathy. Materials and methods: The study was performed on male mice of the BALB/c line (acute toxicity was assessed) and male rats of the Wistar line, which were modeled chronic traumatic encephalopathy by the method of free fall of the load (weight 150 g from a 50 cm height). The injury to rats was reproduced once a day for 7 days. Further, cognitive functions, changes in sensorimotor deficiency, cerebral blood flow, neuron-specific enolase(NSE), S100β, glial fibrillary acidic protein (GFAP) (in blood serum) and β-amyloid, adenosine triphosphate (ATP) (in brain tissue supernatant) were evaluated. Mitochondrial respiration was also measured. Choline alfoscerate (100 mg/kg) was used as a reference drug. Results: The study found that the use of a new pyrimidine derivative contributed to the preservation of the mitochondrial respirometric function and cognitive functions in rats. In addition, against the administration of test-object marked increase in the concentration of ATP, the velocity of cerebral blood flow was 4.2 times (p < 0.05) and 35.6% (p < 0.05), respectively, as well as reduced concentration and GFAP,NSE, S100β, β-amyloid and sensorimotor deficit at 2.7 (p < 0.05) times; 2 times (p < 0.05); 2.4 times (p < 0.05); of 30.4% (p < 0.05 and 46.5% (p < 0.05), respectively. The LD50 (per os) for the test-object was 4973.56 ± 573.72 mg/kg. Conclusion: Based on the obtained data, high therapeutic efficacy and low systemic toxicity of the application are assumed 4-{2-[2-(3,4-dimethoxyphenyl)-vinyl]-6-ethyl-4-oxo-5-phenyl-4H-pyrimidine-1-Il}benzsulfamide in chronic traumatic encephalopathy.

Keywords: chronic traumatic encephalopathy; mitochondrial function; pyrimidine derivatives.

MeSH terms

  • Animals
  • Cerebrovascular Circulation / drug effects
  • Chronic Traumatic Encephalopathy / drug therapy*
  • Chronic Traumatic Encephalopathy / physiopathology
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay / methods
  • Gait Disorders, Neurologic / etiology
  • Gait Disorders, Neurologic / physiopathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mitochondria / drug effects*
  • Pyrimidines / administration & dosage
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use*
  • ROC Curve
  • Ultrasonography, Doppler / methods

Substances

  • Pyrimidines
  • pyrimidine