Cerebroprotective activity of 3-benzylxanthine derivative - compound Ale-15, in conditions of bilateral common carotid arteries ligation (ischemic stroke)

Abstract

INTRODUCTIONIn past years the prevalence growth of cardio-vascular diseases, that includes also cerebrovascular accidents (CVA), was noted. 1 Ischemic brain injuries are followed by serious neuralgic disorders, such as cognitive, motor, verbal impairment and other functions of central nervous system (CNS). 2 Acute ischemic stroke is a leading cause of mortality, morbidity, long-term disability in industrialized countries, and involves a complex array of processes involving multiple biological systems which collectively determine the susceptibility to and outcome from the ischemic event. 3,4 That is why the search for methods for pharmacological correction of these disorders and medications, that decrease degree of neurodegeneration in case of cerebral ischemia, is an essential issue of modern medicinal science.Oxidative stress, defined as the accumulation of reactive oxygen species (ROS) plays a pivotal role in neurodegeneration associated with ischemia, trauma, and other neurodegenerative diseases. [5][6][7][8][9] The accumulation of ROS in neurons results in lipid peroxidation, protein oxidation, DNA damage, and finally cell death. [5][6][7][8][9] Nowadays an active search for new cerebroprotectors is being carried out among compounds, that affect the compensatory shunt of ATP synthesis in conditions of ABSTRACT Background: Acute ischemic stroke is a leading cause of mortality, morbidity, long-term disability in industrialized countries. One of main parts of it pathogenesis is production of reactive oxygen species. The accumulation of them in neurons results in lipid peroxidation, protein oxidation, DNA damage, and finally cell death. Thereby the search of novel drugs, that have antioxidant action and can be used to complex treatment of cerebral strokes is reasonable. It is known, that xanthine derivatives exhibit a broad spectrum of biological activity, including antioxidant. So that, the goal of this research was to study in vivo neuroprotective action of water-soluble derivative of 3-benzylxanthinemorpholin-4-ium 3-benzylxanthinyl-8-methylthioacetate (Ale-15 compound) in comparison with neuroprotector-antioxidant -Mexidol. Methods: Experimental part was done on white Wistar rats of both sexes of 220-260 g weight. For assessment of neuroprotective action of compound we used a model of global incomplete cerebral ischemia, that was reproduced by bilateral common carotid arteries ligation. Results: It was studied an acute toxicity of Ale-15 compound, it influence on survival of laboratory animals, on progression of neuralgic deficit, on the content of adenylic nucleotides, on criteria of energy metabolism, on the activity of antioxidant enzymes and on oxidative modification of protein. Results of study showed, that injection of Ale-15 compound to animals with ischemic stroke intragastrically during 4 days positively reduced death rate and quantity of animals with serious neurologic symptoms. The main parts of Ale-15 cerebroprotective mechanism are antioxidant and anti-ischemic actions. Conclusions: The performe...

Some aspects of neuroprotective action of a new derivative of 3-methylxanthine (compound C-3) under conditions of acute disorder of cerebral circulation (ADCC) modeling by ischemic stroke type

“…Groups of animals NO2 -, mcmol/g of proteine The obtained data are consistent with the results of other researchers that have establish a sharp increase in the concentration of NO in brain of animals with both focal and global ischemia [1][2][3]7,8]. It is known that NO concentration is beginning to rise from the first minutes of ischemia, reaching a maximum on the 1-3 th days [12].…”

“…Indices of oxidative protein modification (OPM) were measured by the method of Halliwell [11] on interaction of oxidized amino acid residues with 2,4-dinitrophenylhydrazones (2.4-DNPH) and formation of aldehydephenylhydrazones (APH) and carboxyphenylhydrazones (CPH) with absorption spectrum at 274 nm 363 nm respectively []. The measurement of SOD activity was conducted with application of phenazine methosulfate and nitroblue tetrazolium [12].…”

Prospective Biological Active Compounds Among 7-Substituted of 3-Benzyl-8-Propylxanthines for Treatment of Metabolic Syndrome Pathologies

“…The attention of scientists who are searching for biologically active substances, is attracted by the natural nitrogen-containing heterocyclic systems [6], and the xanthine derivatives [7,8] occupy a special place in this, among which, as well as several effective non-toxic drugs.…”

Analysis of influence of quantum chemical descriptors on NO-scavenger properties among xanthine derivatives

“…Xanthine derivatives are valuable class of natural organic compounds with wide spectrum of biological properties and pronounced antioxidant activity [3][4][5]9]. In the previous work we described the ability of xanthine derivatives to NO-inhibition [2].…”