Research of energotropic properties of 3-benzylxanthine derivative-prospective neuroprotector

Abstract

Background: Acute cerebrovascular accident (CVA) represent a leading cause of mortality in developed countries. Ischemic stroke results in pronounced structural changes in cerebral tissue, which in turn play a central role in perturbation of cognitive and associative functions of the brain. An outcome of hypoxia is the mitochondrial dysfunction, which manifests in sequential phase changes in mitochondrial enzymatic complexes, and leads to inhibition of aerobic energy synthesis, energy-dependent functions, and cell metabolism. Aims and objectives: The present study was carried out to investigate the energotropic properties of potential neuroprotector – xanthine derivative Ale-15 in conditions of experimental ischemia. Materials and Methods: Experimental part was done on white Wistar rats. For assessment of energotropic propeties of Ale-15 compound we used a model of global incomplete cerebral ischemia. The state of energy metabolism was determined by the level of the most important intermediates – ATP, ADP, AMP and by following indices of energy metabolism: the energy charge, energy potential, coefficient of comparison, index of phosphorylation and thermodynamic respiration control. Results: Xanthine derivative Ale-15 stabilized the energy state of the neurons of animals with CVA, as evidenced by increasing levels of ATP and ADP on the background of decreasing of AMP level. Analysis of additional energy parameters showed, that the compound increased the degree of filling ATP-ADP-AMP system by macroergic bonds, activated the direct reaction of ATP synthesis, corrected the imbalance of ratio of macroergic phosphates and intensity of phosphorylation of adenyl-nucleotide system in generally. All these allowed suggesting, that studied compound Ale-15 possessed energotropic effect in conditions of cerebral ischemia. Conclusion: The present study showed the energotropic properties of xanthine derivative Ale-15 in condition of ischemic stroke, which exceeded the effect of reference drug - Mexidol.