Pharmacological Correction of Thiol-Disulphide Imbalance in the Rat Brain by Intranasal Form of Il-1b Antagonist in a Model of Chronic Cerebral Ischemia
| Autor: | B.S. Burlaka, N. V. Bukhtiyarova, E. V. Suprun, E. G. Aliyeva, I. F. Belenichev, A. S. Simbirtsev, A. M. Ishchenko |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification Nitrotyrosine Glutathione peroxidase Glutathione reductase Antagonist Glutathione Pharmacology Biochemistry Neuroprotection Hsp70 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine chemistry Molecular Biology 030217 neurology & neurosurgery Cysteine |
| Zdroj: | Neurochemical Journal. 15:30-36 |
| ISSN: | 1819-7132 1819-7124 |
| Popis: | —We studied the effect of intranasal administration of RAIL gel (Il-1b antagonist) to rats with experimental chronic cerebral ischemia caused by permanent occlusion of the common carotid arteries on the main parameters of the thiol-disulfide system and the expression of heat shock protein (HSP70) in the brain. It was found that chronic cerebral ischemia leads to disruption of the thiol-disulfide system—a decrease in the activity of glutathione peroxidase (GP), glutathione transferase (GT), and glutathione reductase (GR), a deficiency of reduced thiols and GSH, and a decrease in the content of cysteine and methionine associated with an increase in the oxidized form of glutathione in the brain of animals. In parallel, we found an increase in the content of the nitrosative stress marker, nitrotyrosine, and a decrease in the concentration of the endogenous cytoprotective protein HSP70. Intranasal administration of RAIL for 18 days led to a 58.2% increase in the reduced intermediates of the thiol-disulfide system (SH-group) and a 100% increase in the GSH level, while the content of its oxidized form decreased by 36.3% compared to the control. RAIL increased the activity of GR by 96.1%, GP by 68.1%, and GT by 137.7% relative to control. After the course of intranasal administration of RAIL gel, the concentration of the HSP70 protein in the cytosol of the brain homogenate of animals increased by 98.4%, and in mitochondria by 142.8% compared with the control parameters. Treatment with RAIL has a neuroprotective effect aimed at stabilization of thiol-disulfide equilibrium and activation of HSP70-dependent mechanisms of endogenous neuroprotection. |
| Databáze: | OpenAIRE |
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