RESUMEN

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.

RESUMEN

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.

Asunto(s)

RESUMEN

Cyclooxygenase and lipoxygenase derived lipid metabolites of polyunsaturated fatty acids (PUFAs), as well as their role in the inflammation, have been studied quite thoroughly. However, cytochrome P450 derived lipid mediators, as well as their participation in the regulation of the inflammation, need deeper understanding. In recent years, it has become known that PUFAs are oxidized by cytochrome P450 epoxygenases to epoxy fatty acids, which act as the extremely powerful lipid mediators involved in resolving inflammation. Recent studies have shown that the anti-inflammatory mechanisms of ω-3 PUFAs are also mediated by their conversion to the endocannabinoid epoxides. Thus, it is clear that a number of therapeutically relevant functions of PUFAs are due to their conversion to PUFA epoxides. However, with the participation of cytochrome P450 epoxygenases, not only PUFA epoxides, but also other metabolites are formed. They are further are converted by epoxide hydrolases into pro-inflammatory dihydroxy fatty acids and anti-inflammatory dihydroxyeicosatrienoic acids. The study of the role of PUFA epoxides in the regulation of the inflammation and pharmacological modeling of the activity of epoxide hydrolases are the promising strategies for the treatment of the inflammatory diseases. This review systematizes the current literature data of the fatty acid epoxides, in particular, the endocannabinoid epoxides. Their role in the regulation of inflammation is discussed.

Asunto(s)

RESUMEN

The combined course of bronchial asthma (BA) and obesity is one of the urgent medical and social problems that requires a comprehensive and careful study in connection with a decrease in the quality of life of such patients, an increase in the frequency, duration of hospitalization and a high economic burden for the state as a whole. The relationship between BA and obesity is now confirmed by numerous studies, at the same time, despite the variability of the proposed mechanisms of pathogenetic effects of obesity on asthma, metabolic aspects of the relationship of these diseases need further study. Adipose tissue hormones are responsible for the energy homeostasis of the body therefore, excessive accumulation of adipose tissue is accompanied by the development of an imbalance in metabolic processes in various organs and tissues. Due to the emergence of new scientific data on the role and function of adipokines in the body, metabolic effects of adipokines are considered in the focus of their pathophysiological association with obesity and asthma. This literary review highlights the current understanding of the role of metabolic effects of the most studied adipokines (resistin, retinol-binding protein, leptin and adiponectin) in the development of obesity and BA. Gender and age-dependent features of adipokine levels in BA and obesity are described. Data on the confirmed role of adiponectin and leptin in the progression of BA combined with obesity are presented. It has been shown that the role of resistin and retinol-binding protein in the development of BA combined with obesity has not been studied. It is demonstrated that further study of metabolic activity of adipokines in BA is an actual and perspective direction of researches which will allow to develop new diagnostic and therapeutic strategies in patients with BA with obesity.

RESUMEN

The pathogenesis of age-related diseases such as metabolic syndrome, type 2 diabetes, Parkinson's disease and Alzheimer's disease is associated with oxidative stress and chronic inflammation. Violation of redox homeostasis is accompanied by the development of peroxisome dysfunction and impaired biosynthesis of plasmalogens, which can be closely related to the aging process and the development of age-dependent pathology. Reflecting the functional activity of peroxisomes, plasmalogens can serve not only as potential biomarkers of diseases associated with oxidative stress and aging, but also as an important therapeutic target. The purpose of this review is to analyze the current knowledge of little-studied biological and pathological aspects of plasmalogen participation in the pathophysiology of neurodegenerative and metabolic diseases of older persons. Understanding the role of plasmalogens in the pathophysiology of these diseases can lead to the development of effective diagnostic and prognostic biomarkers, as well as treatment methods for neurodegenerative and metabolic diseases of older people.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

We examined composition of plasma non-esterified fatty acids (NFAs), erythrocyte fatty acids, levels of eicosanoids in patients with asthma and chronic obstructive pulmonary disease (COPD) with different type of the inflammatory response. The results of our study show that asthma and COPD in remission are associated with changes in the composition NFAs of plasma, FA of erythrocytes, level eicosanoid despite the difference in the regulation of immunological mechanisms of systemic inflammation. These changes are characterized by excessive production of arachidonic acid (20:4n-6) and cyclooxygenase and lipoxygenase metabolites (thromboxane B2, leukotriene B4) and deficiency of their functional antagonist, eicosapentaenoic acid (20:5n-3). The recognized association between altered fatty acid composition and disorders of the immune mechanisms of regulation of systemic inflammation in COPD and asthma demonstrated the important role of fatty acids and their metabolites in persistence of inflammatory processes in diseases of the respiratory system in the condition of remission.

Asunto(s)

RESUMEN

The effects of high-fat diet on the thiol disulfide homeostasis of rats were evaluated by activities of glutathione redox system functioning in the blood and liver. A short-term (30 days) high-fat diet inhibited activities of glutathione-dependent enzymes. High-fat loading for 90 days promoted the development of a compensatory response of the glutathione redox system and restoration of the thiol disulfide homeostasis. The compensatory processes in the glutathione system failed on day 180 of alimentary loading because of redox imbalance in the thiol disulfide metabolism.

Asunto(s)

RESUMEN

We studied heme oxygenase-1 expression in rat liver during the development of nonalcoholic steatohepatitis simulated by feeding high-fat ration for 30, 90, and 180 days. Increased number of hepatocytes synthesizing heme oxygenase-1 was demonstrated at all stages of pathology development. Herewith, the intensity of enzyme expression by individual cells was reduced on experimental day 180 during the development of liver fibrosis.

Asunto(s)

RESUMEN

Studied the composition of fatty acids of polar and neutral lipids of plasma, erythrocytes and liver Wistar rats under prolonged high-fat diet. It was established that during long-term (90-180 days) in rats high-fat load is blocking the cells ligand-retseptor active capture polyunsaturated fatty acids (PUFAs) in the low-density lipoprotein (LDL). This is confirmed by the accumulation of blood in LDL cholesterol and lipid fractions, esterified n-3 and n-6 PUFA (triacylglycerides, sterols esters, phospholipids), while the deficit these same fatty acids in the lipids of erythrocytes. In the liver under the influence of prolonged high-fat diet increased pool monoenic (18:1 n-9) and polyunsaturated (20:5 n-3, 20:3 n-6, 22:5 n-3) fatty acids. These data suggest that prolonged exposure of rats high-fat diet contributes to compensatory de novo synthesis of fatty acids in the liver. However, due to violations of the receptor active transport of fatty acids synthesized in the liver fatty acids are not captured by cells of the peripheral organs. Identified data allow us to expand the understanding of the role of nutritional factors in the physiology and pathophysiology of the cell, modulation of lipid metabolism.

Asunto(s)

RESUMEN

We studied liver phospholipid composition and activity of the glutathione redox-system in rats on prolonged for 180 days high-fat diet. The adaptive response was formed from day 30 to day 90 of high-fat load and was associated with increased relative content of phosphatidylseryne and phosphatidylethanolamine homeostasis. Constant antioxidant activity of glutathione redox-system for 30 days period of high-fat load was achieved by stable glutathioneperoxidase activity, on 90th day--level of glutathione reductase increased. The detected fluctuations in phospholipid composition and activity of glutathione redox-system in liver tissue on 30-90th days of the experiment indicated the formation of a compensatory response to maintain cell integrity. On 180th day of high-fat load due to exhaustion of compensatory mechanisms in the glutathione antioxidant defense and intensification of lipid peroxidation the lipid matrix of cytomembrane underwent profound restructuring associated with decreased levels of phosphatidylinositol, phosphatidylethanolamine, increased proportion of apoptotic phospholipids (phosphatidylserine, sphingomyelin). Such phospholipids composition on the background of glutathione redox-system inhibition can determine apoptosis, necrosis and liver fibrogenesis. These results extend the knowledge about mechanisms of liver adaptation and disadaptation to nutritional stress.

Asunto(s)

RESUMEN

The new model of nonalcoholic steatohepatitis in rats is based on alimentary effects of hypercaloric diet including much cholesterol and beef fat. This model reproduces structural and functional disorders in the liver, including hepatocyte fatty degeneration, parenchymatous necrosis and fibrosis paralleled by dyslipidemia and is intended for studies of the mechanisms of formation, progress, and therapy of liver diseases of noninfectious origin.

Asunto(s)

RESUMEN

Erythrocyte phospholipids and lipid fatty acid composition was investigated at different stages of exposure to high-caloric diet in male Wistar rats. The revealed modification of erythrocyte lipids shows specific features of membrane response to stress factors of alimentary nature, in particular, cell protection compensatory mechanism initiation on the 90th day and their depletion by the 180th day of high-caloric diet.

Asunto(s)

RESUMEN

It is investigated conditions of system "lipid peroksidation - antioxidant protection" at rats of the line Wistar at prolonged formation alimentary dyslipidemia (DLP). It is established, that at formation DLP during 46 days in cells there was no increase in resistance and capacity of processes antioxidant protection. In prolonged DLP (90 days) was characterized by occurrence of the compensation-adaptive answer in the system "lipid peroksidation - antioxidant protection".

Asunto(s)

RESUMEN

We studied phospholipid composition of erythrocytes and the state of the glutathione redox system in rats during adaptation to cholesterol load for 180 days. The adaptive response is formed during the period from day 30 to day 90 of cholesterol load and is associated with increased relative content of phosphatidylethanolamine and phosphatidylinositol, activation of glutathione redox system enzymes (glutathione reductase and glutathione peroxidase), and enhanced production of glutathione.

Asunto(s)

RESUMEN

Study character of the redistribution of fatty acids between the lipid fraction of plasma and erythrocytes in rats with prolonged high-fat diet (30, 90, 180 days). Shown that at long high-fat rations in the lipids of erythrocytes decreasing pool polyunsaturated fatty acids (oleic, dihomo-gamma-linoleic, eicosapentaenoic, arachidonic), increases of saturated fatty acids (myristic, stearic) levels. In lipids fractions of plasma revealed the opposite direction of changes in the level of the fatty acids: the accumulation of essential polyunsaturated fatty acids, reduction of saturated fatty acids. Supposedly, that high-fat diet promotes de novo compensatory synthesis of polyunsaturated fatty acids, but disturbed apoB-100 receptor-mediated active transport of fatty acids with low-density lipoproteins (LDL), synthesized in the liver fatty acids is not captured by the cells peripheral organs. Marker of the apoB-100 receptor breach of transfer low-density lipoprotein, transporting polyunsaturated fatty acids was to increase LDL cholesterol in serum.

Asunto(s)

RESUMEN

Gas liquid chromatography was used to analyze the composition of plasma free fatty acids (FA) and erythrocyte lipid FAs in patients with metabolic syndrome (MS) in various glucose-insulin homeostasis. The serum lipids of oxylipins were studied in patients with MS, by applying enzyme immunoassay. The patients with MS in the absence of glucose-insulin homeostatic disorders and those with significant insulin resistance (IR) were found to have accumulation of polyenic FA (18:2 omega6), 18:p omega3, 22:4 omega6) and a decreased pool of saturated FA (12:0, 14:0, 16:0, 17:0) in the plasma with simultaneous polyunsaturated FA (18:3 omega3, 20:4 omega6) with a preponderance of fatty FA (14:0, 18:0) in the red blood cells. The high serum concentrations of leukotriene B, and 6-keto-prostaglandine-F1a, were detectable in the examinees with MS. Increased thromboxane A2 synthesis was observed when the patients with MS developed IR. The findings suggest that there are impairments in the composition of plasma free FA and erythrocyte lipid FA and in the synthesis of oxylipins in patients with MS.

Asunto(s)

RESUMEN

We used liquid chromatography for analysis of fatty acids (FA) in lipids of erythrocytes of patients with hypertensive disease (HD) with normo- (group 1) and hyperlipidemia (group 2). Abnormalities of FA composition of erythrocyte lipids were revealed in both groups. In group 1 we found deficit of polyenic acids of omega-6 family, accumulation of Mead acid - prostanoid precursor with pronounced vasoconstrictor and pro inflammatory properties. In group 2 we noted more profound rearrangement of lipid matrix of erythrocyte membrane manifested as deficiency of omega-3 polyenic acids, accumulation of palmitinic and arachidonic acids. Preponderance of saturated FA in erythrocytes and deficiency of polyenic acids might evidence for pathology of their ligand-receptor transport into the cell. Blockade of active FA transport initiates formation of HD, promotes accumulation of atherogenic fractions of lipoproteins in blood. These results evidence for important pathogenetic role of FA in development of hypertension.

Asunto(s)

RESUMEN

The impact of different doses of food biologically active additive (BAA) on base lipid sea-hydrobions on the condition of water-electrolyte and nitrogen metabolism, proteinosynthesis and hepatobiliary functions of liver has been studied for rats with the experimental cardio-vascular pathology. BAA is the lipid fraction from schoolmaster gonate squid Berryteuthis magister liver, containing 10% of polyunsaturated fatty acids (PUFA) and 50% of alkyldiacylglycerides. In relation to organism's emunctory systems in conditions of experimental cardio-vascular pathology the biotropic dose makes 1 g/kg daily. BAA acts negatively in dose 2 g/kg daily. It is conditioned by aggravation of electrolyte imbalance, lowering of excretion and reabsorption of sodium, potassium, magnesium, metabolites of purine and nitrogen metabolism, stimulation of intoxication and calcification processes, load effect on proteinosynthesis function of rats liver.

Asunto(s)