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The review presents evidence of the participation of low-density lipoproteins (LDL) modified by low molecular weight dicarbonyl compounds formed during freeradical oxidation of lipids (malondialdehyde) and carbohydrates in the development of endothelial dysfunction and atherosclerotic vascular lesions. The authors believe that it is they, and not oxidized (hydroperoxide-containing) LDL, that are the main factors of pathogenesis. The role of dicarbonyl-modified LDL in LOX-1 dependent induction of processes leading to the development of endothelial dysfunction is discussed. The results of studies proving that damage to the glycocalyx (a layer of macromolecules that prevent the development of endothelial dysfunction) covering the luminal surface of the endothelium is caused by hyperproduction of reactive oxygen species. Ways of pharmacological correction of free-radical oxidation processes are discussed, due to which inhibition of atherogenesis and diabetogenesis can be achieved.

Diabetes mellitus remains one of the most pressing problems in the 21st century. The research objective was to study the level of glycotoxins and oxidation-reduction potential of a serum/cell at the complicated and uncomplicated course of diabetes mellitus type 2 was and find the ways to correct the disorder. Materials and methods. There were three groups of patients aged from 55 up to 70 years, a total of 80 people. The main group (group No. 3) was presented by 40 men suffering from a diabetes mellitus type 2 with a macrovascular disease of the lower extremities. Depending on the chosen remedy and the carried-out therapy, patients of the first group were sectioned into subgroups on 20 people, in the 2nd subgroup additionally N-acetylcysteine solution was introduced in a daily dose of 600 mg once, intravenously, within 7 days. Definition of the studied indicators was made by HPLS methods, prior to therapy, for the third and seventh day. Results. Obtained data confirm activation of polyol pathway of glucose disintegration. Antioxidant potential of the serum and cells decreases. Using N-acetylcysteini in complex therapy reduces implications of carbonyl and oxidative stresses, due to multiple decrease of the final products of glycation. Conclusions. When identifying the presented indicators in patients with diabetic macroangiopathy of the lower extremities, the administration of N-acetylcysteine, intravenously in a daily dose of 600 mg (7 days course) is recommended.

We have suggested that the molecular mechanism of vascular wall damage in diabetes is not substantially different from that in atherosclerosis. Thus, it can be assumed that aldehyde-modified LDL should be eliminated from the blood stream with much greater speed than non-oxidized LDL. In the available literature there is information about the clearance of native human LDL from the bloodstream, whereas information on the clearance of the aldehyde-modified LDL in animals or humans was not found. Based on this, the present work is devoted to the clearance of aldehyde-modified LDL of rabbits and humans introduced into the bloodstream of rabbits. We investigated the clearance of glyoxal-, methylglyoxal- and MDA-modified LDL from the bloodstream of rabbits. We used biotinylated LDL of rabbit blood plasma and FITC-labeled LDL of human blood plasma. LDL was isolated with preparative ultracentrifugation in NaBr gradient. It was shown that glyoxal- and methylglyoxal-modified LDL of rabbits and humans circulated in the bloodstream for the same time as native LDL while MDA-modified LDL was rapidly eliminated from the bloodstream. The data obtained indicated the possibility of greater atherogenic potential of glyoxal- and methylglyoxal-modified LDL as they circulate in the bloodstream for a rather long time. At the same time, MDA-modified LDL is likely to be exposed to enhanced elimination by macrophages after their "linkage" to blood cells.

The possible involvement of the methylglyoxal and proline accumulation in leaves and roots of three pistachio rootstocks, cv. Sarakha, Abareqi and Bane baghi, pre-inoculated with arbuscular mycorrhizal fungus (Glomus mosseae) in response to salt stress was studied during a greenhouse experiment in 2013. Six months old pistachio seedlings were exposed to four salinity levels of irrigation water (EC of 0.5 as control, 5, 10 and 15 dS m-1) for 70 days. Methylglyoxal and proline of the roots and leaves were increased by increasing salt stress. The highest concentrations of proline in leaves and roots were recorded in Abareqi rootstock while the lowest concentration was observed in Sarakhs. In general, a negative relationship was obtained between proline and methylglyoxal concentrations in both tissues especially at two highest levels of salinity. A very strong relationship between salinity and measured biochemical markers were found. The level of both biomarkers were reduced in both tissues and in all rootstocks as the effect of mycorrhizal symbiosis. Root colonization percentage was declined as the effect of salinity in Abareqi and Bane baghi and not in Sarakhs.

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If a lot of carbohydrates cannot be in vivo stored as glycogen, the synthesis of palmitic fatty acid (FA) from glucose and its adipocyte deposition as triglycerides are under way in phylogenesis. With impaired biological function of exotrophy (fasting, early postnatality, hibernation), the cells perform a reverse process - the synthesis of glucose from FA. Physiologically, the substrate of gluconeogenesis is acetyl-CoA that is converted by the malate → piruvate → glucose pathway in the glyoxalate cycle. Under the pathological conditions of hypoxia and energy deficiency, gluconeogenesis occurs without ATP consumption via the methylglyoxalate pathway (MGP) while using as a substrate of ketone bodies: butyric acid (butyrate) → β-hydroxybutyrate → acetoacetate → acetone → acetol → methylglyoxal (MG) → S-D-lactolglutathione → D-lactate → piruvate → D-lactate. Under physiological conditions, this pathway of gluconeogenesis does not work. The authors hold that gene expression and gluconeogenesis occur via the MGP when glucose levels are low in the cell cytosol (glycopenia) and FA cannot be oxidized in the mitochondria. Cytosol, intercellular medium, plasma show elevated levels of MG and D-lactate, to which it converts under the action of glyoxalases I and II. Glycopenia develops in fasting, diabetes mellitus, metabolic syndrome, renal failure, phenofibrate therapy, impaired function of exotrophy - excessive dietary intake of saturated and trans fatty acids. The chemical interaction of MG with amino acid residues of lysine and arginine leads to protein denaturation during carbonylation - glycosylation and impaired biological function of endoecology. The determination of plasma MG and D-lactate may be a test for glycopenia, compensatory activation of gluconeogenesis from FA or for the evaluation of endogenous intoxication.

The elimination kinetics of carbonyl-modified low density lipoproteins (LDL) from rabbit bloodstream was studied using isolated LDL of rabbits and humans after preliminary biotinylation or labeling with FITZ. LDL from rabbit or human blood plasma were isolated using differential ultracentrifugation in a density gradient, and then LDL were labeled using biotinylation or FITZ, after which they were modified with various low molecular weight natural dicarbonyls: malondialdehyde (MDA), glyoxal or methylglyoxal. Native and dicarbonyl-modified biotinylated or FITZ-labeled LDL were injected into the ear vein of rabbits and blood samples were taken at certain intervals. To determine the content of biotinylated LDL in blood plasma, an enzyme immunoassay was performed; FITZ-labeled LDL were determined by spectra fluorescence. It is shown that glyoxal- and methylglyoxal-modified LDL in rabbits and humans circulated in the bloodstream for almost the same time as native (unmodified) LDL. At the same time, MDA-modified rabbit and human LDL were extremely quickly eliminated from the rabbit bloodstream. Dicarbonyl-modified LDL from the donors blood plasma were not associated with the red blood cells and endothelial cells. It has been shown that using the kits Oxidized LDL ELISA ("Mercodia", Sweden), it is possible to identify mainly MDA-modified LDL. The level of MDA-modified LDL in the blood plasma of CHD patients sharply decreases during therapy with the hypocholesterolemic drug the PCSK9 inhibitor (evulokumab), which activates LDL reutilization in the liver cells. These results explain the extreme drop in the level of MDA-modified LDL by their increased utilization in hepatocytes. The results obtained indicate a high atherogenicity of glyoxal- and methylglyoxal-modified LDL, long-term circulating in the bloodstream.