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.
The aim of the paper is to assess the change in the mitochondrial respirometric function under conditions of various pathologies.Materials and methods. The study was performed on male Wistar rats. Experimental focal cerebral ischemia, traumatic brain injury, coronary occlusive myocardial infarction and muscle dysfunction were used as pathological models. Focal ischemia was reproduced by the method of irreversible thermocoagulation of the middle cerebral artery. Traumatic brain injury was modeled by the method of free fall of the load. Experimental myocardial infarction was reproduced by ligating the descending branch of the left coronary artery. Muscle dysfunction was modeled by the method of «forced swimming with a 20% burden». The respiratory function of mitochondria was assessed by the method of respirometry by the change in oxygen consumption when introducing mitochondrial respiration into the medium: Oligomycin, Rotenone and FCCP. Additionally, we evaluated the intensity of the glycolysis process and the activity of respiratory complexes I, II, IV and V. In order to comprehensively assess the respiratory function, an ELISA study was conducted to determine the concentration of ATP, mitochondrial ATP synthetase, cytochrome C oxidase and NADP-Oxidase 4.Results. In the course of the study it was established that under conditions of experimental cerebral ischemia, traumatic brain injury, myocardial infarction and muscle dysfunction, the ATP-generating ability of mitochondria the maximum breathing and respiratory capacity deteriorated, herby the decrease in overall respiratory function was accompanied by an increase in glycolysis, which was uncompensated, as well as dysfunction of mitochondrial complexes I, II, IV and V, confirmed by an increase in NADPH oxidase 4 activity and a decrease in cytochrome C oxidases and ATP synthetase. As a result, the observed changes in mitochondrial respiration function contributed to a decrease in ATP concentration under conditions of cerebral ischemia - by 3.2 times (p <0.05), traumatic brain injury – by 2.6 times (p <0.05), myocardial infarction – by 1.8 times (p <0.05) and muscle dysfunction – by 4 times (p <0.05).Conclusion. Basing on the data obtained, we can assume that in conditions of cerebral ischemia, traumatic brain injury, myocardial infarction and muscle dysfunction, there is deterioration of the mitochondrial respirometric function with inhibition of ATP synthesis and increased glycolysis.
Nowdays it is established that ischemic brain damage like ischemic stroke is one of the leading cause of death and disability in the population that assumes relevance development of anti-ischemic drugs. The work studied the anti-hypoxic and anti-ischemic effect of 7 plant extracts. Antihypoxic activity was assessed on models of hypobaric, hypercapnic, histotoxic, hematotoxic hypoxia. Anti-ischemic activity of test-extracts was studied on the focal cerebral ischemia model. Administration of Tagetes patula, Gaillardia pulchella, Sorbaria sorbifolia, Grossularia reclinata, Ribes nigrum, Rubus caesius and Lysimachia punctata extracts contributed to the necrosis zone reduction by 56.6% (p<0.05); 37.3% (p<0.05); 73.2% (p<0.05); 49.4% (p<0.05); 42.5% (p<0.05); 85.5% (p<0.05); 44.2% (p<0.05) and also restored aerobic metabolism in brain tissue. Test -objects increased of the animal lifespan under hypoxia conditions. Based on the data obtained, it is assumed that further studies of North Caucasus flora plant extracts as cerebro-protective agents are promising.Resumen: Hoy en día, se ha establecido que el daño cerebral isquémico, como el accidente cerebrovascular isquémico, es una de las principales causas de muerte y discapacidad en la población lo cual hace relevante el desarrollo fármacos antiisquémicos. En este trabajo se estudió el efecto antihipóxico y antiisquémico de siete extractos de plantas. La actividad antihipóxica se evaluó en modelos de hipoxia hipocrática, hipercápnica, histotóxica y hematotóxica. La actividad antiisquémica de los extractos de prueba se estudió en el modelo de isquemia cerebral focal. La administración de los extractos de Tagetes patula; Gaillardia pulchella; Sorbaria sorbifolia; Grossularia reclinata; Ribes nigrum; Rubus caesius y Lysimachia punctata contribuyeron a la reducción de la zona de necrosis en un 56,6% (p<0,05); 37,3% (p<0,05); 73,2% (p<0,05); 49,4% (p<0,05); 42,5% (p<0,05); 85,5% (p<0,05); 44.2% (p<0.05), respectivamente, además, de restaurar el metabolismo aeróbico en el tejido cerebral. Comparado con el control, se observó un aumento en el tiempo de sobrevida del animal en condiciones de hipoxia. Sobre la base de los interesantes datos obtenidos, se sugiere estudios adicionales de extractos de plantas de la flora del Cáucaso Norte como agentes protectores del cerebro. Palabras clave: Isquemia cerebral; Extracto de plantas; Cáucaso norteRecibido |
The aim of the study is to evaluate the effect of pumpkin (Cucurbita pepo L.) and marigold extracts (Tagetes patula L.) on the hippocampal mitochondria functional activity within the conditions of experimental acute brain hypometabolism.Materials and methods. The work was performed on 50 male Wistar rats, which reproduced an acute brain hypometabolic state by administration of a 3M sodium azide solution in hippocampus (n = 40 and n = 10 – a group of sham-operated animals). The test extracts and the reference drug – EGb 761 – were prophylactically administered at the dose of 100 mg/kg per os for 10 days. 24 hours after the last administration, sodium azide was injected, the brain was taken, the hippocampus was isolated to obtain a supernatant and determine the parameters of mitochondrial respiration, the intensity of anaerobic processes, the concentration of the apoptosis-inducing factor, endonuclease G, and β-amyloid.Results. The carried out study established that the prophylactic administration of pumpkin and marigold extracts contributed to the restoration of a mitochondrial function and a decrease in the intensity of anaerobic processes. In the group of the rats treated with pumpkin and marigold extracts, an increase of ATP concentration in the hippocampal supernatant by 65.7% (p<0.002) was observed; it was 66.2% (p><0.002) relative to the animals deprived of pharmacological support. ,When the rats were treated with pumpkin and marigold extracts, a decrease in the concentration of apoptosis-inducing factor (by 33% (p><0.002) and 38.3% (p><0.002), respectively) and endonuclease G (by 3.6 times (p><0.002) and 4.4 times (p><0.002), respectively) was also noted. The administration of pumpkin and marigold extracts reduced the amyloid β-peptide concentration in the rats’ hippocampus by 54.4% (p><0.0002) and 54.4% (p><0.0002), respectively. The test-extracts had an equivalent therapeutic efficacy with the reference drug. Conclusion On the basis of the obtained data, it is possible to suggest the prospect of a further study of pumpkin and marigold extracts as the drugs of a targeted correction of cerebral hypometabolism. Keywords: plant extracts, hypometabolism, hippocampus, mitochondria >< 0.002) was observed; it was 66.2% (p<0.002) relative to the animals deprived of pharmacological support. ,When the rats were treated with pumpkin and marigold extracts, a decrease in the concentration of apoptosis-inducing factor (by 33% (p><0.002) and 38.3% (p><0.002), respectively) and endonuclease G (by 3.6 times (p><0.002) and 4.4 times (p><0.002), respectively) was also noted. The adm>< 0.002) relative to the animals deprived of pharmacological support. ,When the rats were treated with pumpkin and marigold extracts, a decrease in the concentration of apoptosis-inducing factor (by 33% (p<0.002) and 38.3% (p><0.002), respectively) and endonuclease G (by 3.6 times (p><0.002) and 4.4 times (p><0.002), respectively) was also noted. The administration of pumpki>< 0.002) and 38.3% (p<0.002), respectively) and endonuclease G (by 3.6 times (p><0.002) and 4.4 times (p><0.002), respectively) was also noted. The administration of pumpkin and marigold extracts reduced the amyloid β-peptide concentration in the rats’ hippocampus by 54.4% (p><0.0002) and 54.4% (p><0.0002), respectively. The test-extracts had an equivalent therapeutic efficacy with >< 0.002), respectively) and endonuclease G (by 3.6 times (p<0.002) and 4.4 times (p><0.002), respectively) was also noted. The administration of pumpkin and marigold extracts reduced the amyloid β-peptide concentration in the rats’ hippocampus by 54.4% (p><0.0002< 0.002) and 4.4 times (p<0.002), respectively) was also noted. The administration of pumpkin and marigold extracts reduced the amyloid β-peptide concentration in the rats’ hippocampus by 54.4% (p><0.0002) and 54.4% (p><0.0002), respectively. The te>< 0.002), respectively) was also noted. The administration of pumpkin and marigold extracts reduced the amyloid β-peptide concentration in the rats’ hippocampus by 54.4% (p<0.0002) and 54.4% (p><0.0002), respectively. The test-extracts had an equiva>< 0.0002) and 54.4% (p<0.0002), respectively. The test-extracts had an equivalent therapeutic efficacy with the reference drug. Conclusion On the basis of the obtained d>< 0.0002), respectively. The test-extracts had an equivalent therapeutic efficacy with the reference drug.Conclusion On the basis of the obtained data, it is possible to suggest the prospect of a further study of pumpkin and marigold extracts as the drugs of a targeted correction of cerebral hypometabolism.
Chronic traumatic encephalopathy (CTE) is a severe neurodegenerative disease that can affect people of all ages and professions. The aim of the study was to study the effects of drugs of different pharmacological groups on the course of CTE. Materials and methods. The pathology model was reproduced by dropping a 150 g load from a height of 0.5 m onto the parietal region of the rat skull for 7 days. Results. Based on the results of the experiment, the restoration of cognitive functions and a decrease in the concentration of markers of neurodegradation was established with the use of Cerepro, Panthogam, Hypoxene, Stimol, Phenibut. Conclusions: having analyzed the experimental data, it is possible to assume the presence of cerebroprotective activity in the studied drugs and the possibility of their use in the treatment of chronic traumatic encephalopathy.
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