Vol 26, No 6 (2023)

Relevance. Oxidative stress, resulting from an imbalance between ROS production and the antioxidant defense system, is a major disruption of chronic inflammation in OA and obesity. It should be noted that the study and understanding of OS and their relationship with the identification of joint tissues is necessary to develop new therapeutic approaches to the occurrence and expediency of the metabolic phenotype of OA.

Aim. To study protein oxidative modification (OMP) and reserve-adaptive potential in patients with the metabolic phenotype of osteoarthritis (OA).

Material and methods. Participants were divided into 2 groups: Control group - patients without articular pathology, metabolic syndrome. The experimental group consisted of patients with the metabolic phenotype of OA. The subjects were collected complaints and anamnesis, as well as general clinical and orthopedic examination. In the blood serum, indicators of OMP and superoxidedismutase (SOD) were determined. Patients were asked to answer the questions of clinical scales of the functional state of the joints and quality of life.

Results. The initial activity of blood serum SOD was somewhat lower in patients with the metabolic phenotype of OA, and the level of OMP showed certain differences in the levels of activity of the processes of spontaneous and metal-catalyzed PMB. The total area under the spontaneous OMP curve was statistically significantly higher (p<0,01), mainly due to the neutral fraction of aldehyde dinitrophenyl hydrozones (ADNFH). The level of reserve-adaptive potential was statistically significantly lower than the control group. An inverse correlation was found between the total area, the area of ADNFH of metal-catalyzed OMP and the level of pain, which indicates higher levels of oxidative stress in patients with severe clinical symptoms.

Сonclusion. In patients with pronounced indicators of clinical manifestations of OA, more active processes of redox changes were observed. There was a decrease in the activity of antioxidant activity and the level of reserve-adaptive potential.

Ferroptosis is an iron-dependent non-apoptotic form of regulated cell death. In 2012, the anti-cancer activity of erastin was shown, based on the induction of a new type of cell death, which is prevented by iron chelators and lipophilic antioxidants. The term "ferroptosis" has been proposed to characterize this iron-dependent, non-apoptotic form of cell death. The purpose of this work is to evaluate and classify the range of compounds capable of inducing ferroptosis in various cell types.

Glutathione (GSH), a common intracellular antioxidant, is required for the activity of various antioxidant enzymes (eg, GPX4). Erastine inhibits the uptake of cystine by the cystine/glutamate antiporter, creating a defect in the cell's antioxidant defenses and leading to iron-dependent oxidative death.

GPX4 is a selenium-containing enzyme that catalyzes the reduction of organic hydroperoxides and lipid peroxides by reduced glutathione. The study revealed two promising compounds, named RSL3 and RSL5 by the authors.

Tert-butyl hydroperoxide (t-BuOOH) is such a lipid peroxide analog and is widely regarded as a lipid peroxidation stimulant. Exposure to t-BuOOH resulted in a ferrostatin-1 and liprostatin-1 sensitive increase in lipid peroxidation.

An excess of non-heme iron (Fe2+ and Fe3+) causes ferroptosis. Live/dead cell viability analysis showed that Fe(III)-citrate, erastin and RSL3 induce cell death. Co-treatment with ferrostatin-1, an inhibitor of ferroptosis, inhibited cell death.

Other materials can cause ferroptosis by inducing lipid peroxidation. Mitochondrial DNA damaging drugs such as zalcitabine induce autophagy-dependent ferroptosis in human pancreatic cancer cells. The implementation of the model of cell death in the form of ferroptosis is highly dependent on the state of cellular metabolism and degradation systems, such as autophagy, which form a complex network for the formation of oxidative stress. Pharmacological induction of ferroptosis is a promising direction in cancer chemotherapy.

Relevance. Alzheimer's disease is a terminal form of dementia with a complex pathogenesis in which NOX-dependent oxidative stress plays an extremely important role.

Aim of the study. To evaluate the influence of oxycinnamic acids on the alteration of NOX4 activity in brain tissue of animals with experimental Alzheimer's disease.

Material and methods. Alzheimer's disease was modeled in Wistar rats by injection of β-amyloid aggregates with amino acid sequence 1-42 into hippocampal tissue (CA1 segment). Oxycinnamic acids: caffeic acid, coumaric acid, ferulic acid and synapic acid were administered at a dose of 100 mg/kg, orally for 60 days after the Alzheimer's disease model. Ethylmethylhydroxypyridine succinate was used as a reference drug in a similar dosage and dosing mode. Changes in the concentration of active NOX4 isophrome, hydrogen peroxide as well as β-amyloid in brain tissue of rats were assessed after the indicated time period.

Results. This study showed that the analyzed oxycinnamic acids were comparable with each other and the referent. Thus, a statistically significant (p<0.05) decrease of NOX4, hydrogen peroxide and β-amyloid concentrations was observed against the background of the studied substances application relative to the untreated animals. Correlation analysis showed that there was a strong correlation (r= 0.96968) between changes in β-amyloid and NOX4 content. Also a strong correlation relationship is observed in the case of analysis of changes in β-amyloid and hydrogen peroxide concentration (r=0,97060).

Conclusion. On the basis of the obtained data, it may be assumed that the use of oxycinnamic acids decrease the activity of NOX4, resulting in reduced formation of peroxides and, as a consequence, oxidative stress. At the same time, reduction of oxidative processes intensity leads to decrease of β-amyloid content in brain tissue.

Relevance. Astaxanthin occurs naturally in free and esterified form. An important distinguishing property of astaxanthin esters is their great stability during storage, heating and oxidation. It is possible to obtain a substance with an optimal set of physical, chemical and biological characteristics by improving the method of synthesis of the active molecule, which is rationally carried out by mathematical methods.

The purpose of the study is to optimize the method for the synthesis of astaxanthin ester and benzoic acid by the method of mathematical planning of the experiment.

Material and methods. The influence of the synthesis parameters on the yield of the ester of astaxanthin and benzoic acid, β,β-carotene-4,4'-dione-3,3'-dibenzoate, was evaluated by the method of mathematical planning of the experiment, using the construction of a mathematical model based on the first-order regression equation.

Results. The steep ascent method was used to determine the optimal parameters for the synthesis of β,β-carotene-4,4'-dione-3,3'-dibenzoate. The maximum yield of the target product – β,β-carotene-4,4'-dione-3,3'-dibenzoate was achieved at a synthesis temperature of 60°C, a reaction time of 4.5 hours, a biocatalyst amount of 0.5 g, and a stirring speed of 55 rpm.

Conclusions. Using the construction of a mathematical model and the search for optimal conditions using the steep climb method, we managed to increase the yield of the target synthesis product – β,β-carotene-4,4'-dione-3,3'-dibenzoate from 50% in the initial conditions to 65%, and also to reveal the influence of all considered factors on the synthesis process. The data obtained on the basis of the conducted studies by the method of mathematical planning of the experiment suggest that the optimal yield of β,β-carotene-4,4'-dione-3,3'-dibenzoate is achieved if the synthesis is carried out at 60°C for 4.5 hours, with a stirring speed of 55 rpm and in the presence of 0.5 g of the Novozyme 435 biocatalyst. During the experiment, it was found that an additional optimization parameter to be introduced into the model could be the “number of biocatalyst use cycles”. However, at the moment it cannot be taken into account in the mathematical model, because this property of the enzyme refers to uncontrolled optimization factors.

Relevance. It is known the method of quantitative determination of the total flavonoids in the herb of common yarrow (Achillea millefolium L.) included in the State Pharmacopoeia of the Russian Federation XIV edition, according to which at the stage of extraction of these raw materials should be acid hydrolysis with ethyl alcohol 96% containing 1% hydrochloric acid concentrated, followed by determination of the amount of flavonoids in recalculation on luteolin. The flavonoid glycosides, including 7-O-glucosides luteolin (cynaroside) and apigenin (cosmosiin), difficult to acid hydrolysis, which does not allow for complete hydrolysis and exhaustive extraction of the target substances. Determination of the main groups of biologically active substances by thin-layer chromatography (TLC) involves the use of a standard sample of sudan III, not contained in the raw material.

The purpose of this study is the improvement of methods of qualitative and quantitative analysis of herb of Achillea millefolium L.

Material and methods. Yarrow herb harvested in 2021 was used as study materials. Extraction of individual substances from yarrow herbs was carried out using column chromatography on silica gel KSC 50/100 under conditions of gradient elution with chloroform-ethanol solvent mixture in different ratios. Along with the isolated individual flavonoids, we used working standard samples of flavonoids obtained by the authors in previous studies of herbal plants containing flavonoids, characterized using UV and NMR spectroscopy: rutin, quercetin, kaempferol, cynaroside, luteolin. Flavonoid content was determined by thin-layer chromatography and by differential spectrophotometry.

Results. TLC analysis revealed the presence of three dominant and diagnostically significant flavonoids: cosmosiin, cynaroside and apigenin. Analysis of UV spectra also confirmed that the spectral characteristics of the water-alcoholic extracts from common yarrow herbs, especially under the conditions of differential spectrophotometry, are mainly determined by the dominant flavones (cosmosiin, cynaroside and apigenin).

Conclusions. The obtained results of studies on the flavonoid composition and spectral characteristics of the isolated dominant flavonoids suggest the feasibility of conducting of the qualitative and quantitative analysis of common yarrow herbs using cynaroside as a standard sample.