Effect of the water-soluble cholesterol-methyl-β-cyclodextrin complex on the development of pulmonary edema with an analysis of the osmotic resistance of erythrocytes in rats

Author:

Kobzar N. E.1,Mikhailov V. P.1,Porseva V. V.1

Affiliation:

1. Yaroslavl State Medical University

Abstract

Introduction. Methyl-β-cyclodextrin is a potent acceptor of cellular membrane cholesterol and, at the same time, used as a solubilizer, which makes it a potential target for targeted delivery of hydrophobic compounds.Aim. To assess the effect of administration of methyl-β-cyclodextrin containing cholesterol on the degree of lung hydration and osmotic resistance of erythrocytes against the background of pulmonary edema in adult rats caused by the administration of mezaton.Materials and methods. We investigated the degree of hydration of the lungs by the value of the pulmonary coefficient and their dry residue. Osmotic resistance of erythrocytes were assessed by the intensity of their hemolysis in a series of hypotonic sodium chloride solutions in adult male Wistar rats (220±40 g) of the control group (intact, n=10) and two experimental groups with pulmonary edema caused by the administration of mezaton (n=10) and with the subsequent introduction of a water-soluble complex cholesterol-methyl-β-cyclodextrin against the background of the development of pulmonary edema (n=10). We used additional criteria for assessing the osmotic resistance of erythrocytes: minimum resistance – the concentration of sodium chloride solution, at which the first “weak” erythrocytes begin to hemolyze; maximum resistance is the concentration of sodium chloride solution at which all or almost all erythrocytes hemolyzed.Results. The introduction of mezaton led to the development of pronounced hemolysis and hydration of the lungs with the development of their edema and a narrowing of the range of minimum and maximum osmotic resistance of erythrocytes. The introduction of a complex of cholesterol with methyl-β-cyclodextrin after edemogenic exposure led to a decrease in the severity of pulmonary edema, determined by a decrease in the pulmonary coefficient and an increase in the dry residue, and to an increase in the osmotic resistance of erythrocytes with an expansion of the range of their minimum and maximum osmotic resistance.Conclusion. The introduction of a water-soluble complex of cholesterol with methyl-β-cyclodextrin against the background of the development of hemodynamic pulmonary edema significantly reduced the degree of hydration of the lungs, which combined with an increase in the osmotic resistance of erythrocytes.

Publisher

Far Eastern Scientific Center Of Physiology and Pathology of Respiration

Subject

General Medicine

Reference12 articles.

1. Mikhailov V.P. Pathogenesis of pulmonary edema. Yaroslavl; 2002 (in Russian).

2. Minasyan M.N. Influence of dehydration, hyperbaric oxygenation, their combined effect on the state of lipid metabolism and the development of neurogenic pulmonary edema (experimental study): abstract of PhD thesis. Moscow; 2003 (in Russian).

3. Karpunin D.V., Akimov S.A., Frolov V.A. Formation of pores in planar lipid membranes containing lisolipids and cholesterol. Biologicheskie membrany 2005; 22(5):429–432 (in Russian).

4. Rassler B. Contribution of α- and β- Adrenergic Mechanisms to the Development of Pulmonary Edema. Scientifica(Cairo) 2012; 2012:829504. https://doi.org/10.6064/2012/829504

5. Janz D.R., Ware L.B. The role of red blood cells and cell-free hemoglobin in the pathogenesis of ARDS. J. Intensive Care 2015; 3:20. https://doi.org/10.1186/s40560-015-0086-3

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