Morphofunctional characterization of rat thymus mast cells after administration of magnesium orotate mechanically activated forms

Relevance. The topicality of the work is determined by the wide spread of hypomagnesemia among the people, which makes it necessary to correct it. The aim of the work is to elucidate the cell-mediated response of the thymus mastocytic link to magnesium deficiency and its correction by the mechanoactivated form of magnesium orotate. Materials and Methods . Animals with drug-induced magnesium deficiency (administration of furosemide 30 mg/kg for 14 days) were administered either the initial preparation Magnerot (Magnerot, Vervag Pharma, Germany), or its mechanoactivated form. The level of magnesium in the blood was determined by test systems ARKREY (Japan). The concentration of magnesium in the thymus tissue was determined by the method of emission spectroscopy with inductively coupled (argon) plasma on an atomic emission spectrometer. Density of mastocytes and the indices of degranulation and granulolosis were calculated on paraffin sections of the thymus after coloration with toluidine blue. Results and Discussion . It was shown that furosemide administration the amount of magnesium decreased in the blood (from 1,750,08 to 0,9020,18 mmol/l, p0,05), but increased in the thymus (from 1,60,6 in the control to 3,71,2 mg/l); in the gland tissue, the number of mastocytes of morphotype A decreased and the number of mastocytes of morphotype D, after active degranulation, increased (by 7,1 times, p0,05). The type of mastocyte secretion in hypomagnesemia is represented by the merocrine variant. The administration of the initial magnesium orotate led to an increase in the concentration of magnesium in the blood to 1,150,25 mmol/l, which is 65,7% of the initial level, the amount of magnesium in the thymus remained elevated (3,41,1 mg/l), the number of actively degranulating cells (morphotype D) was increased. Mechanoactivated magnesium orotate restored the concentration of Mg2+ in the blood to 89,1% (1,560,18 mmol/l, p0,05) and decreased in the thymus (to 2,30,7 mg/l), restored the subpopulation of mastocytes saturated with heparin (type A), reduced the number of mastocytes of morphotype D. Conclusion . The mechanoactivated form of magnesium orotate has a normalizing effect on the population of thymic mastocytes, shows pronounced immunomodulatory activity, which allows us to consider it as a potential therapeutic agent for clinical testing in the complex therapy of hypomagnesemia and associated immunodeficiency.

Effects of Magnesium Orotate, Benfotiamine and a Combination of Vitamins on Mitochondrial and Cholinergic Function in the TgF344-AD Rat Model of Alzheimer’s Disease

Glucose hypometabolism, mitochondrial dysfunction, and cholinergic deficits have been reported in early stages of Alzheimer’s disease (AD). Here, we examine these parameters in TgF344-AD rats, an Alzheimer model that carries amyloid precursor protein and presenilin-1 mutations, and of wild type F344 rats. In mitochondria isolated from rat hippocampi, we found reductions of complex I and oxidative phosphorylation in transgenic rats. Further impairments, also of complex II, were observed in aged (wild-type and transgenic) rats. Treatment with a “cocktail” containing magnesium orotate, benfotiamine, folic acid, cyanocobalamin, and cholecalciferol did not affect mitochondrial activities in wild-type rats but restored diminished activities in transgenic rats to wild-type levels. Glucose, lactate, and pyruvate levels were unchanged by age, genetic background, or treatment. Using microdialysis, we also investigated extracellular concentrations of acetylcholine that were strongly reduced in transgenic animals. Again, ACh levels in wild-type rats did not change upon treatment with nutrients, whereas the cocktail increased hippocampal acetylcholine levels under physiological stimulation. We conclude that TgF344-AD rats display a distinct mitochondrial and cholinergic dysfunction not unlike the findings in patients suffering from AD. This dysfunction can be partially corrected by the application of the “cocktail” which is particularly active in aged rats. We suggest that the TgF344-AD rat is a promising model to further investigate mitochondrial and cholinergic dysfunction and potential treatment approaches for AD.

Systematic Analysis of the Roles of Trace Elements in the Prevention and Treatment of Chronic Heart Failure

Systematic analysis of 3 728 publications on the relationship between microelement status and chronic heart failure (CHF) was carried out. Three main areas of research have been identified: 1) magnesium, electrolytes and CHF; 2) the transcriptional and antioxidant effects of zinc, selenium, copper; 3) iron-deficiency anemia and CHF. In this paper, we consider a complex of relationships between the magnesium insufficiency and CHF, the effect of magnesium on vascular tone, mitochondria, heart rhythm and the susceptibility of cardiomyocytes to adrenergic stimulation. Using magnesium orotate for the treatment of CHF is a feasible approach to compensate magnesium insufficiency in patients with CHF.

Characteristics of the Population of the Rat Thymus CD68+ Cells in Response to Tautomeric Forms of Magnesium Orotate Introduction under Simulated Magnesium Deficiency

he aim of study was to identify a response of the thymus CD68+ cells population to the introduction of tautomeric forms of magnesium orotate under magnesium deficiency.Material and methods. Magnesium-deficient status in rats was simulated by furosemide loading (30 mg/kg 14 days); then the animals were injected magnesium orotate in the initial oxo-form (Magnerot©, Vervag, Germany) and hydroxy-form obtained by mechanical activation, dosage 50 mg/kg, for 14 days., The density of thymocytes and macrophages was calculated in the subcapsular zone, cortex and brain matter (stained with hematoxylin and eosin) in the thymus, macrophages were studied immunohistochemically using monoclonal CD68 antibodies (Clone PG-M1).Results. The oxo-form of the drug was shown to lead to an increase in the number of CD68+ cells in the cortex of thymus (1.7 compared with the control) and medulla of thymus (2.3 times), an increase in the intensity of immunofluorescence (22.5%), the appearance of the thymus lobule of large CD68+cells in the cortex and the medulla part with a clearly traced intracellular localization of granules. The introduction of mechanically activated hydroxyl-form was accompanied by an increase in the number of CD68+ macrophages in the cortical area (1.5 times), and cortico-medullary partition (in 1.4 times), but did not affect the cerebral area of the thymus. The overall intensity of fluorescent staining reduced to 27.87±2.2 relative units (RU).Conclusion. The tautomeric forms of magnesium orotate have a diverse effect on the macrophage population of the thymus: the introduction of the oxo-form is accompanied by a significant activating effect on the CD68+macrophages in contrast to the hydroxyl form having a moderate modulating effect.