The Role of Hydroxyeicosatetraenoic Acids in the Regulation of Inflammation in Bronchial Asthma.

Hydroperoxyeicosatetraenoic acids (HETEs) are metabolites of arachidonic acid that are oxidized by a family of enzymes including cyclooxygenase, lipoxygenase, and cytochrome P450 enzymes. These enzymes are widely present in various organs and tissues, and the HETEs they synthesize perform an important function in the regulation of immune reactions and haemostasis processes under physiological and pathophysiological conditions. More researchers confirm the role of these oxidized metabolites in modulating inflammation in asthma. The high production of HETEs in allergic and severe asthma indicates their involvement in the processes of an acute inflammatory response. On the other hand, disturbance of the metabolic transformation of arachidonic acid contributes to the development of chronic inflammation due to insufficient synthesis of mediators that resolve inflammatory processes. Several HETEs have both pro-inflammatory and anti-inflammatory effects, which underscores the ongoing interest in their involvement in the pathogenesis of asthma. At the same time, research results are scarce. Based on an analysis of the literature, the pathways of metabolic transformation of 5-HETE, 12-HETE, and 15-HETE with the participation of cyclooxygenases, lipoxygenases, and cytochrome P-450, as well as their role in asthma pathogenesis, were discussed. The PubMed database was searched for information covering the last five years using selected inclusion criteria. Information queries included the following set of keywords: "bronchial asthma, hydroxyeicosatetraenoic acids, 5-HETE, 12-HETE, 15-HETE." Literature data indicate that the role of HETEs in human physiology and pathology, including the modulation of inflammation in asthma, requires comprehensive study to selectively modulate the enzymatic pathways of arachidonic acid metabolism leading to the production of these mediators.

Molecular species of glycerophosphoethanolamines in obesity-associated asthma.

Bronchial asthma (BA) complicated by obesity is a progressive disease phenotype that hardly responds to standard therapy. In this regard, it is important to elucidate cellular and molecular mechanisms of development of this comorbid pathology. In recent years, lipidomics has become an active research tool, opening new opportunities not only for understanding cellular processes in health and disease, but also for providing a personalized approach to medicine. The aim of this study was to characterize the lipidome phenotype based on the study of molecular species of glycerophosphatidylethanolamines (GPEs) in blood plasma of patients with BA complicated by obesity. Molecular species of GPEs were studied in blood samples of 11 patients. Identification and quantification of GPEs was carried out using high resolution tandem mass spectrometry. For the first time in this pathology, a change in the lipidome profile of molecular species of diacyl, alkyl-acyl and alkenyl-acyl HPEs of blood plasma was shown. In BA complicated by obesity, acyl groups 18:2 and 20:4 were dominated in the sn2 position of the molecular composition of diacylphosphoethanolamines. Simultaneously with the increase in the level of GPE diacyls with the fatty acids (FA) 20:4, 22:4, and 18:2, there was a decrease in these FAs in alkyl and alkenyl molecular species of GPEs, thus indicating their redistribution between subclasses. The eicosapentaenoic acid (20:5) deficiency at the sn2 position of alkenyl GPEs in patients with BA complicated by obesity indicates a decrease in the substrate for the synthesis of anti-inflammatory mediators. The resulting imbalance in the distribution of GPE subclasses, due to a pronounced increase in the content of diacyl GPE under conditions of the deficiency of molecular species of ether forms, can probably cause chronic inflammation and the development of oxidative stress. The recognized lipidome profile characterized by the modification of the basic composition and the chemical structure of GPE molecular species in BA complicated by obesity indicates their involvement in the pathogenetic mechanisms underlying BA development. The elucidation of particular roles of individual subclasses of glycerophospholipids and their individual members may contribute to the identification of new therapeutic targets and biomarkers of bronchopulmonary pathology.

[The influence of sinusoidal modulated currents on the fatty acid composition of plasma and blood erythrocytes in the patients presenting with chronic cholecystitis]. / Vliyanie sinusoidal'nykh modulirovannykh tokov na sostav zhirnykh kislot plazmy i eritrotsitov krovi u patsientov s khronicheskim kholetsistitom.

The objective of the present study was to evaluate the effectiveness of the treatment with sinusoidal modulated currents on lipid metabolism in the patients presenting with chronic cholecystitis in the state of remission. PATIENTS AND METHODS: The study included 25 patients with chronic non-calculosis cholecystitis in phase of remission and 20 healthy subjects (controls). We studied the serum lipid spectrum as well as the fatty acid composition of plasma and blood erythrocytes before and after therapy with sinusoidal modulated currents applied to the right-sided hypochondrium region. RESULTS AND DISCUSSION: The treatment of the patients with chronic cholecystitis in remission with the use of sinusoidal modulated currents produced moderate lipid-modulatory and membranotropic effects mediated through the activation of the processes of lipid metabolism that may result in the depletion of the pool of essential polyunsaturated fatty acids. CONCLUSION: The results of this study give evidence that it is advisable to treat the patients presenting with chronic cholecystitis by sinusoidal modulated currents in the combination with the oral intake of exogenous polyunsaturated fatty acids.

[Blood fatty acids in the development and correction of metabolic syndrome]. / Zhirnye kisloty krovi v formirovanii i korrektsii metabolicheskogo sindroma.

AIM: to investigate the composition of plasma fatty acids (FA) and red blood cells and the level of eicosanoids in patients with metabolic syndrome (MS) and to assess whether metabolic disturbances may be corrected during a cycle use of an ω-3 polyunsaturated fatty acid (PUFA). SUBJECTS AND METHODS: Examinations were made in 46 patients, including Group 1 (a control group) of 15 persons without MS components; Group 2 of 31 patients with MS, Group 3 of 16 MS patients who had taken an ω-3 PUFA for 6 months, and Group 4 of 15 MS patients who had received the drug for 12 months. The composition of plasma FA and red blood cells was analyzed on a gas-liquid chromatograph. An enzyme immunoassay was used to measure the serum levels of tumor necrosis factor-α (TNF-α) and eicosanoids (thromboxane B2, 6-keto-prostaglandin F1α, leukotriene B4). A biologically active additive from the king crab (Paralithodes camtschatica) hepatopancreas was used as a source of ω-3 PUFA. RESULTS: Having a higher proportion of linoleic and α-linolenic acids in the plasma, the patients were found to have decreased levels of ω-3 and ω-6 PUFAs (linoleic and α-linolenic, arachidonic, and eicosapentaenoic acids) and a larger proportion of Mead acid and saturated FAs (myristic and stearic acids) in the red blood cells, suggesting that that cellular blood FA transfer was impaired and FAs were absorbed by cells. Their serum samples showed the high levels of leukotriene B4, 6-keto-prostaglandin F1α, and thromboxane A2. The long-term (6- and 12-month) use of ω-3 PUFA from the king crab hepatopancreas had a positive impact in modifying the lipid FA composition of red blood cells and in eliminating deficiencies of physiologically important ω-3 and ω-6 PUFAs in the blood cells. CONCLUSION: The findings suggest that FAs and their metabolites play an important role in the pathogenesis of MS and that dietary ω-3 PUFA should be incorporated into a package of preventive and therapeutic measures for MS.

[MORPHO-FUNCTIONAL CHARACTERISTICS OF BLOOD CELL MITOCHONDRIA IN BRONCHIAL ASTHMA].

We undertook a structural and functional study of blood cell mitochondria in 25 patients with controlled mild bronchial asthma (BA) including evaluation of blood saturation with oxygen, carboxyhemoglobin level in blood and carbon monoxide content in the exhaled air. Membrane potential of leukocyte mitochondria was determined based on the results of flow cytofluorimetry and fatty acid (FA) composition in platelet mitochondrial membranes measured by GLC. It was shown that the absence of clinical symptoms of BA during remission was associated with a reduction of membrane potential and a change of FA composition resulting in the depletion of the basal pool of saturated (12:0, 14:0, 18:0) and polyunsaturated (20:4n-6, 20:5n-3, 22:5n-3, 22:4n-6) FA. These changes in the structural and functional state of blood cell mitochondria in patients with BA are signs of disordered energy-producing activity, membrane permeability and transmembrane transport suggesting the development of mitochondrial dysfunction and cellular hypoxia. A deeper insight into the role of the structural and functional state of blood cell mitochondria in the formation of respiratory disorders will facilitate early detection of the risk and complications of bronchial obstruction.