VDAC1-DEPENDENT MITOCHONDRIAL EFFECTS OF COMPOUNDS CONTAINING THE 4-HYDROXY-3,5-DI-TRETBUTYL PHENYL SUBSTITUENT IN EXPERIMENTAL FOCAL CEREBRAL ISCHAEMIA

DOI: https://doi.org/10.29296/24999490-2023-03-08

Pozdnyakov
Pyatigorsk Medical and Pharmaceutical Institute, Kalinin Ave., 11. Pyatigorsk, Stavropol Region, 357532, Russian Federation

Introduction. Ischemic stroke is one of the most common causes of mortality and primary disability. The treatment of ischemic stroke, especially its complications, includes neuroprotective agents among which correctors of mitochondrial dysfunction stand out. Aim of the study. To evaluate VDAC1-dependent mitochondrial effects of compounds containing 4-hydroxy-3,5-di-tretbutyl phenyl substituent in experimental brain ischemia. Material and methods. Brain ischemia was modeled in Wistar rats by irreversible thermocoagulation of middle cerebral artery. After ischemia modeling, the tested compounds (7 objects) and reference drug ethylmethylhydroxypyridine succinate were administered orally (once in day) for 72 hours. After that time, the changes in concentration of ATP, apoptosis-inducing factor, caspase-3, mitochondrial hydrogen peroxide and VDAC1 in brain tissue were assessed in animals. Results. In a study, were shown that the administration of studied compounds in animals with focal ischemia increased the ATP concentration while decreasing the content of mitochondrial hydrogen peroxide and the activity of caspase-dependent and caspase-independent apoptosis reactions. There was also found a decrease of VDAC1 concentration in animals treated with the analyzed compounds, which correlated with the changes of ATP concentration (r=0,89714), apoptosis-inducing factor (r=0,92367) and mitochondrial hydrogen peroxide (r=0,87629). Conclusion. It was concluded that mitochondrial effects of compounds containing 4-hydroxy-3,5-ditrebutyl phenyl which manifested as decreased generation of mitochondrial reactive oxygen species, decreased intensity of reactions of internal apoptosis pathway and increased ATP concentration, were connected with the effect of these compounds on VDAC1 channel activity.
Keywords: 
schemic stroke, neuroprotection, mitochondrial dysfunction, VDAC1
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