THE IMPACT OF DIAMIDE DERIVATIVES OF OXALIC ACID ON FREE RADICAL LIPID OXIDATION IN WHITE RAT BRAIN AND LIVER.

Antioxidants are widely used in medicine due to their ability to bind free radicals - active biomolecules that destroy the genetic apparatus of cells and the structure of their membranes, which makes it possible to reduce the intensity of oxidative processes in the body. In a living organism, free radicals are involved in various processes, but their activity is controlled by antioxidants. The purpose of this work was to conduct a series of studies to identify the antioxidant activity of new synthesized compounds of a series of oxalic acid diamides in the brain and liver tissue of white rats in vivo and in vitro experiments, as well as to determine their potential pharmacological properties. The studies were conducted on outbred white male rats, weighing 180-200 g, kept on a normal diet. After autopsy, the brain and liver were isolated, washed with saline, cleared of blood vessels, and homogenized in Tris-HCl buffer (pH-7.4) (in vitro). The research results showed significant antioxidant activity (AOA) of all compounds with varying effectiveness. The most pronounced activity was demonstrated by compound SV-425 in both brain and liver tissues. Compound SV-427 demonstrated the least activity, with levels in brain tissue and liver tissue. In addition, all physicochemical descriptors of the studied compounds comply with Lipinski's rule of five to identify new molecules for the treatment of oxidative stress. From the data obtained, it can be concluded that the studied compounds have antioxidant properties, helping to protect cells from oxidative stress. This is important for the prevention and treatment of diseases associated with increased levels of free radicals.

SYNAPTIC PROCESSES IN THE ANTINOCICEPTIVE SOMATOSENSORY CORTEX SI OF THE BRAIN ACTIVATED BY THE VENTRAL POSTERIOR-LATERAL THALAMIC NUCLEUS IN A ROTENONE MODEL OF PARKINSON'S DISEASE.

This study aimed to investigate the ratio of excitatory and depressor post-stimulus manifestations of SI single neuron activity during VPL stimulation of the thalamic nucleus in a PD model to identify excitotoxicity in neurodegeneration and the formation of persistent pain, which is poorly treatable. Electrophysiological studies were performed on 6 albino rats (230±30 g): intact (n=3) and rotenone model (n=3) of Parkinson's disease (PD) induced by unilateral administration of rotenone for 4 weeks (n=3). We performed extracellular recordings of spike activity of 207 single neurons in the primary somatosensory cortex (SI) of the ventral posterolateral thalamic nucleus (VPL). Changes in depressor and excitatory responses (TD and TP), accompanied by post-tetanic depression and potentiation, were detected using the analysis. A significant excess in the frequency of the prestimulus (background) activity of SI neurons in a PD model was revealed as a result of the inevitable development of excitotoxicity. At the post-stimulus level, excitotoxicity under pathological conditions should also be recognized. In conclusion, the PD model revealed excitotoxicity in the SI neurons with the emergence of persistent chronic pain.

SYNAPTIC PROCESSES IN PERIAQUEDUCTAL GRAY UNDER ACTIVATION OF LOCUS COERULEUS IN A ROTENONE MODEL OF PARKINSON'S DISEASE.

The aim of the study was investigation the ratio of excitatory and depressor post-stimulus manifestations of Periaqueductal gray (PAG) single neuron activity during Locus coeruleus (LC) stimulation in a Parkinson's disease (PD) model to identify excitotoxicity in neurodegeneration and the formation of persistent pain, which is poorly treatable. The electrophysiological studies were performed on 6 Albino rats (230±30g.): intact (n=3) and on the rotenone model of Parkinson's disease (PD) induced by unilateral injection of rotenone for 4 weeks holding of animals (n=3). The extracellular on-line registration of spike activity of 236 single neurons of the Periaqueductal gray (PAG) at high frequency stimulation (HFS) of Locus coeruleus (LC) in intact animals (116 neurons) and on the model of PD (120 neurons) was produced. According to programmed mathematical analyses were detected changes in depressor and excitatory responses (TD and TP), accompanied by post-tetanic depression and potentiation. In the neurons PAG at HFS LC on the model of PD the full suppression of synaptic depressor poststimulus manifestations of activity, accompanied by posttetanic and the prevalence of such excitatory has been revealed. Was the conclusion about serious neurodegenerative damage of the important antinociceptive structure - PAG, that promotes resistant chronic pain in parkinsonian patients.