This review is devoted to modern systems of nanocarriers that ensure the targeted delivery of flavonoids to various organs and systems. Flavonoids have wide range of effects on the human body due to their antioxidant, anti-inflammatory, antitumor, antimicrobial, antiplatelet and other types of activity. However, the low bioavailability of flavonoids significantly limits their practical application. To overcome this disadvantage, serious efforts have been made in recent years to develop nanoscale carriers for flavonoids. This is particularly important in view of the known antitumor effect of these compounds, which allows them to target tumor cells without affecting surrounding healthy tissues. Nanocarriers provide increased penetration of biologicals into specific organs in combination with controlled and prolonged release, which markedly improves their effectiveness. This review summarizes data on the use of phytosomes, lipid-based nanoparticles, as well as polymeric and inorganic nanoparticles; their advantages and drawbacks are analyzed; the prospect of their use is discussed that opens new possibilities for the clinical application of flavonoids.
The review discusses some of the causes of proteinuria in nephrotic syndrome due to extrarenal mechanisms. Autoantibodies identified in recent years are involved in the violation of the selective permeability of the filtration barrier in membranous nephropathy. The direct relationship between the level of hyperglycemia and proteinuria in diabetic nephropathy is analyzed. The role of reactive oxygen species, end products of glycation, angiotensin II, transforming growth factor β-1, epithelial-mesenchymal transformation of podocytes, Rho GTPases, intracellular signaling pathway mTOR, Wnt/β-catenin signaling cascade is emphasized. Particular attention is paid to the problem of searching and identifying circulating permeability factors in the pathogenesis of idiopathic nephrotic syndrome in patients with minimal changes and focal segmental glomerulosclerosis: vascular permeability factor (VPF), vasodilator-stimulated phosphoprotein (VASP), soluble hemopexin (Hpx) receptor-receptor-receptor type (suPAR), cardiotropin-like cytokine-1 (CLCF-1) and anti-CD40 antibodies. It is noted that the role of such factors is not in doubt today, however, from the standpoint of evidence-based medicine, this role needs serious confirmation by specially formulated criteria.
The literature review is devoted to the study of the mechanisms of the cardioprotective action of a new class of glucose-lowering drugs glyflozins, which inhibit the joint transport of sodium and glucose in the proximal renal tubules. The large-scale clinical trials carried out in recent years have demonstrated the beneficial effect of these compounds not only on glycemic control, but also on the progression of heart failure in patients with diabetes mellitus. Analysis of literature data shows that the effect under consideration is due to both the positive systemic cardiovascular and direct cardiotropic action of the drugs. The first part of the review examines the systemic effect of drugs, including their diuretic, natriuretic and antihypertensive effects, increased hematocrit, vascular effects that influence arterial stiffness, smooth muscle tone, and endothelial dysfunction. The metabolic effects of type 2 sodium and glucose co-transport inhibitors are discussed separately, including an increase in lipolysis, the role of glucagon and activation of ketogenesis, and their contribution to the development of a probable cardioprotective effect.
The review is devoted to the consideration of the nephroprotective effect and its mechanisms in new hypoglycemic drugs gliflozins, identified in largescale randomized placebo-controlled trials and experimental studies. It was found that inhibition of sodium-glucose co-transporter 2 (SGLT2) in the proximal tubules of the kidneys when using these drugs not only leads to a decrease in blood glucose levels, a decrease in blood pressure, body weight, and uric acid content in blood plasma but also delays the progression of chronic kidney disease, inhibiting the development of diabetic nephropathy. This beneficial effect is multifactorial. It is caused by the diuretic and natriuretic effects, a decrease in albuminuria, a decrease in glucotoxicity in the cells of the renal tubules, a hemodynamic effect on kidney function, and a direct anti-inflammatory effect. It is discussed why the use of SGLT2 inhibitors restores tubuloglomerular feedback, which is disrupted in the initial period of diabetic nephropathy and leads to hyperfiltration in the remaining nephrons. Information is provided on the restoration of impaired mitochon drial function due to the positive effect of drugs on the ionic composition of renal tubule cells. This greatly contributes to the enhancement of autophagy, the lysosome-mediated pathway of degradation and removal of damaged organelles, and normalizes intracellular homeostasis. The probable mechanism of autophagy enhancement through increased activity of energy deprivation sensors of AMPK and SIRT1 cells is considered. Possible mechanisms of development of anti-inflammatory and antioxidant action of SGLT2 inhibitors through inhibition of inflammasome activity are discussed. The question of the possible use of gliflozins in chronic kidney disease, the pathogenesis of which is not associated with diabetes mellitus, is considered.
The literature review is devoted to the study of the mechanisms of the cardioprotective action of a new class of glucose-lowering drugs glyflozins, which inhibit the joint transport of sodium and glucose in the proximal renal tubules. Favorable changes in ion transport in cardiomyocytes with the use of these drugs are considered. The inhibition of the activity of the sodium-hydrogen exchanger (NHE) was found, followed by a decrease in the activity of Na+/ Ca2+ exchange on the mitochondrial membranes of the cardiomyocytes, which leads to a decrease in the concentration of Ca2+ in the cytoplasm with a simultaneous increase in mitochondria. This initiates a number of intracellular signaling cascades that contribute to the optimization of mitochondrial homeostasis. The use of glyflozins, apparently, provides a balance between the fusion and fission of mitochondria, which determines the bioenergetic adaptation of the cell to the state of intracellular metabolism, weakens the development of the inflammatory response, fibrosis and oxidative stress in the myocardium, which are activated under conditions of diabetes mellitus. The point of view is discussed, according to which the mechanism of anti-inflammatory action of glyflozins is associated with inhibition of the activity of the NLRP3 inflammasome, which contributes to the progression of myocardial dysfunction and subsequent chronic heart failure. The results of clinical trials and experimental data on the beneficial effect of glyflozins in the development of various phenotypes of heart failure with reduced and preserved ejection fraction are analyzed. The assumption is substantiated about the prospects for wider use of these hypoglycemic drugs in heart failure, which is not limited to diabetes mellitus. The assumptions made require further experimental and clinical studies.
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