Effect of Phosphatidylcholine Nanosomes on Phospholipid Composition of the Plasma Membranes in Liver Cells and Blood Ser

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GY AND PATHOPHYSIOLOGY Effect of Phosphatidylcholine Nanosomes on Phospholipid Composition of the Plasma Membranes in Liver Cells and Blood Serum in Experimental Atherosclerosis G. F. Leskova1, A. P. Kaplun2, D. A. Bezrukov2, and A. I. Lvovsky2

Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 170, No. 8, pp. 143-147, August, 2020 Original article submitted November 11, 2019 Alimentary atherosclerosis is associated with a significant decrease in the content of phosphatidylcholine, the phospholipid that provides antioxidant protection, in the plasma membrane of liver cells, while the level of phosphatidic acid that initiates generation of superoxides, on the contrary, increases. The level of membrane phosphatidylserine, a target of the scavenger receptors, which initiates removal of damaged cells and modified lipoproteins from the circulation was also elevated. In the blood serum of rabbits receiving an atherogenic diet, the content of cardiolipin involved in the immune mechanisms of atherosclerosis development and a risk factor for thrombosis, sharply increased. The level of lysophosphatidylcholine that mediates initiation and progression of atherosclerosis increased. The content of phosphatidylinositol that is involved in the mechanisms protecting from exposure to excess cholesterol was significantly reduced. Treatment of alimentary atherosclerosis with “empty” phosphatidylcholine nanosomes eliminates the key factors initiating atherosclerosis development. Key Words: phospholipids; plasma membrane; liver; atherosclerosis; phosphatidylcholine nanosomes

The development of new methods for the therapy of atherosclerosis still remains a pressing problem. At the same time, insufficient understanding of the fundamental mechanisms of atherosclerosis development limits the possibility of creating effective and safe drugs for this disease. Here we studied the pathogenetic mechanisms underlying cell dysfunction in the liver, the organ that plays the key role in lipid metabolism, during alimentary atherosclerosis. Considering the important role of membrane phospholipids (PL) in controlling the basic 1 Research Institute of General Pathology and Pathophysiology, Moscow, Russia; 2M. V. Lomonosov Institute of Fine Chemical Technology, MIREA — Russian University of Technology, Moscow, Russia. Address for correspondence: [email protected]. G. F. Leskova

cellular processes, we studied the mechanisms of atherogenic changes in the PL composition of liver cell plasma membranes and the possibility of correcting these changes by administration of “empty” phosphatidylcholine nanosomes. The possibility of liposomal correction of atherogenic shifts in the PL composition of blood serum was also studied.

MATERIALS AND METHODS Experiments were performed on 26 male rabbits weighing 3.0±0.2 kg and kept under standard vivarium conditions. Control animals fed a standard diet and received grated carrot in a daily amount of 100 g for 2 months. Two experimental groups received carrot with cholesterol (Ch) in a dose of