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Membranous Aspects OF sarcoma-45 Pathogenesis THERAPY
Ghazaryan PA, Galoyan GM
Yerevan State University, Department of Pharmacology
Haematological Center MH RA, Nersisyan st. 7, 375014 Yerevan, Armenia;
E-mail: ghazarpa@yahoo.com The State of phospholipid and protein Components of erythrocyte membranes has been investigated In white Rats with sarcoma-45. It has been established a disturbance of membranous lipids` metabolism, in particular phospholipids (PL), with is expressed by over double increase in the content of lysophosphatidyl cholines (LPC), phosphatidylinosites (PI), phosphatidylserines (PS) and multiple increase in the level of phosphatidic acids (PA) on the background (Almost thriple) Decrease In the levels of phosphatidylcholines (PC), phosphatidylethanolamines (PE) (p <0.01), sphingomielines (SPM) (p <0.001). As a result of the above mentioned shifts there occur significant changes in PL / PL ratios. The coefficient of LPC / PC increases by 7.3 times, and the PC / PA, on the contrary - decreases by 5.7 times, with testifies to the inhibition of phosphatidogenesis processes, as well as of the phosphatidogenesis processes, as well as of the activation of their destruction. The stated changes are caused by activation of phospholipase A2 and processes of free radical oxidation of ensymatic systems activation of the initial stages of phosphatidogenesis (glicerine kinase, cytoplasmatic glicerophosphate dehydrogenase). The activity of lipid peroxidation brings to disturbance of membrane-connected processes, shift of the activity of lipid-dependent enzymatic system. The cause of it is the increase in the activity of transport enzymatic systems, particularly Na / K- and Mg-ATPases bringing naturally to disturbance of membrane permeability at development of sarcoma-45. After application of cyan-containing derivative of lactone (2-cyan-3,4,4-trimethyl-2-buten-4-olid) there is observed a definite normalization of almost all studied indices. Moreover, it is observed a marked tendency to normalization of the levels of cytotoxic and membranolytic LPC (p <0.01) with simultaneous significant rise of PC content (p <0.001). Concentration of PA, PI, SPM and DPG nearly completely normalizes. The preparation has a positive effect on the activity of transport ATPase, with may certainly bring to a deficite recovery of the processes of permeability of ioms and substances of blood lymphocyte plasmatic membranes. The problem of possible pathogenetic therapy of sarcoma-45 by inclusion of cyan-containing derivatives of lactone into the complex of therapeutic means is discussed.
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