ABSTRACT
This paper reports the results of a study of the impact of the agmatine treatment on erythrocyte resistance to acid hemolytic, reticulocyte count and reticulocyte production index, erythrocyte surface architectonics in streptozotocin-induced diabetic rats. Our results indicate that treatment of diabetic rats with agmatine causes a suppression of erythropoiesis and increases the resistance of erythrocytes against HCl-induced hemolysis. It was shown a 10% increase in the number of young red blood cells and 35% reduction in the number of structurally transformed erythrocytes that are capable of restoring normal biconcave disc shape under physiological condition. Our data demonstrate an improvement of morphofunctional state of red blood cells in diabetes and reflect the positive effect of agmatine treatment on erythrone due to the glucose-lowering action.
Subject(s)
Agmatine/therapeutic use , Diabetes Mellitus, Experimental/drug therapy , Erythrocytes/drug effects , Erythroid Precursor Cells/drug effects , Erythropoiesis/drug effects , Agmatine/administration & dosage , Animals , Blood Glucose/analysis , Decarboxylation , Diabetes Mellitus, Experimental/blood , Erythrocyte Count , Erythrocytes/physiology , Erythroid Precursor Cells/physiology , Male , Rats , StreptozocinABSTRACT
The effects of agmatine on oxidative and nonoxidative metabolic pathways of L-arginine were investigated both in plasma and erythrocytes under experimental diabetes mellitus. It was indicated, that agmatine prevents the development of oxidative-nitrosative stress in diabetic rats. After treatment of animals by agmatine NO-synthase methabolic pathway of L-arginine is depressed whereas arginase one increases in erythrocytes of rats with experimental diabetes mellitus.
Subject(s)
Agmatine/therapeutic use , Antioxidants/therapeutic use , Arginase/blood , Arginine/blood , Diabetes Mellitus, Experimental/drug therapy , Nitric Oxide Synthase/blood , Animals , Blood Glucose/analysis , Diabetes Mellitus, Experimental/blood , Erythrocytes/drug effects , Erythrocytes/metabolism , Male , Nitrates/blood , Nitric Oxide/blood , Nitrites/blood , Ornithine/blood , Rats , StreptozocinABSTRACT
It is shown that reduction of beta,D-galactosyl-containing carbohydrate determinants ofglycoconjugates on theplasmatic membrane of segmentonuclear neutrophills of peripheral blood under type 1 diabetes mellitus (DM) is correlated with changes in aggregation of these cells and may cause their functional disorder. Changes in the parameters of ricin-induced neutrophil activation after inhibition of the phosphatidylinositol-3'-kinase (PI-3'-kinase) enzyme with wortmannin indicated that the functional state ofpolymorphonuclear leukocytes is mediated by signaling pathways in which PI-3'-kinase is involved. Thus, PI-3'-kinase-dependent signal networks are involved in the processes of signal transduction through galactosyl-containing glycoprotein receptors into neutrophilic leukocytes. Inertness of the intensity formation in time ofneutrophil granulocyte cell response on RCA-induced translocation of the p85alpha regulatory subunit of PI-3'-kinase from the cytosolic to the membrane fraction under type 1 DM is a consequence of changes in the number or structure of plasmatic galactosyl-containing glycoprotein receptors. The revealed changes may be etiologic premise of diabetic complications and chronic diseases that impair the functional condition of patients with type 1 DM.
Subject(s)
Class Ia Phosphatidylinositol 3-Kinase/metabolism , Diabetes Mellitus, Type 1/metabolism , Neutrophils/metabolism , Plant Lectins/pharmacology , Receptors, Mitogen/chemistry , Androstadienes/pharmacology , Case-Control Studies , Cell Aggregation/drug effects , Cell Membrane/drug effects , Cell Membrane/metabolism , Cells, Cultured , Cytosol/drug effects , Cytosol/metabolism , Diabetes Mellitus, Type 1/pathology , Humans , Neutrophil Activation/drug effects , Neutrophils/drug effects , Neutrophils/pathology , Protein Kinase Inhibitors/pharmacology , Protein Transport/drug effects , Receptors, Mitogen/metabolism , Signal Transduction/drug effects , WortmanninABSTRACT
The influence of wortmannin and sialospecific lectins on the translocation of p85alpha regulatory subunit of phosphatidylinositol-3'-kinase (PI-3'-kinase) between membrane and cytosolic fractions of the mononuclear and polymorphonuclear leukocytes in healthy donors and patients with type 1 diabetes mellitus (DM) was investigated. It was found out that under type 1 DM PI-3'-kinase takes active part in the transduction of lectin-induced signal through membrane glycoprotein receptors that contain terminal sialic acids linked to subterminal carbohydrate residues with (alpha2-->6) glycosidic bond.
Subject(s)
Cell Membrane/metabolism , Diabetes Mellitus, Type 1/enzymology , Leukocytes/enzymology , Phosphatidylinositol 3-Kinase/metabolism , Protein Subunits/metabolism , Receptors, Cell Surface/metabolism , Signal Transduction/drug effects , Adult , Androstadienes/pharmacology , Blotting, Western , Cell Fractionation , Cell Membrane/drug effects , Cytosol/metabolism , Diabetes Mellitus, Type 1/pathology , Electrophoresis, Polyacrylamide Gel , Enzyme Activation/drug effects , Glycoproteins/metabolism , Humans , Insulin/metabolism , Lectins/pharmacology , Leukocytes/drug effects , Leukocytes/pathology , Phosphoinositide-3 Kinase Inhibitors , Protein Kinase Inhibitors/pharmacology , Protein Subunits/antagonists & inhibitors , Sialic Acids/chemistry , Sialic Acids/metabolism , WortmanninABSTRACT
Diameter, the surface area of lymphocytes and their nuclea as well as the reserve potential and regulatory properties of lymphocytes membranes in control rats, in rats with experimental diabetes mellitus before and after administration of L-arginine and aminoguanidine were investigated. Significant difference in size and the membrane fund of lymphocytes in animals with experimental diabetes mellitus was detected. In control lymphocytes, the membrane fund was 70% while during diabetes mellitus it was 40%. Such a difference might be one of the reasons of changes in properties and functional state of lymphocytes in diabetes. Administration of L-arginine and aminoguanidine to diabetic animals caused positive effect: the volume of lymphocytes diminished and the regulatory membrane properties of these cells became better.
Subject(s)
Arginine/pharmacology , Cell Membrane/drug effects , Diabetes Mellitus, Experimental/blood , Guanidines/pharmacology , Lymphocytes/drug effects , Animals , Cell Culture Techniques , Cell Membrane/physiology , Cell Size , Cells, Cultured , Lymphocytes/cytology , Lymphocytes/physiology , Male , Rats , Rats, WistarABSTRACT
In experimental streptozotocin-induced diabetes, the activity of enzymes which have common substrate (L-arginine) changes in leucocytes of peripheral blood. It leads to misbalance between different pathways of arginine metabolism: NO-synthase (oxidative) pathway is activated, whereas arginase (nonoxidative) one is depressed. The injection of L-arginine under diabetes activated nonoxidative pathway, which can be seen in possible decrease in NO-synthase activity with unchanged arginase activity. After injection ofaminoguanidine in animals under diabetes the efficiency of both pathways in leucocytes decreases, which may be the basis of reconstitution of physiological pool to the relatively essential amino acid L-arginine.
Subject(s)
Arginine/metabolism , Diabetes Mellitus, Experimental/metabolism , Leukocytes/metabolism , Animals , Arginase/antagonists & inhibitors , Arginase/metabolism , Arginine/administration & dosage , Arginine/pharmacology , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/enzymology , Guanidines/administration & dosage , Guanidines/pharmacology , Leukocytes/enzymology , Male , Nitric Oxide/biosynthesis , Nitric Oxide Synthase Type II/antagonists & inhibitors , Nitric Oxide Synthase Type II/metabolism , Rats , Rats, Wistar , Substrate SpecificityABSTRACT
It was shown that administration of aminoguanidine is accompanied by a decrease of the content of nitric oxide stable metabolites, as well as protein carbonyl groups in leukocytes and blood plasma in diabetic and control animals. Aminoguanidine is proposed to be used for pharmacological correction of NO biosynthesis. Aminoguanidine, being the selective iNOS inhibitor, antioxidant and the factor eliminating post-translational protein nitrozylation and oxidative modification, weaken the toxic effects of NO and positively modulates the pathological state caused by NO hyperproduction.
Subject(s)
Diabetes Mellitus, Experimental/metabolism , Glycation End Products, Advanced/metabolism , Guanidines/pharmacology , Nitric Oxide/biosynthesis , Oxidative Stress/drug effects , Proteins/metabolism , Animals , Diabetes Mellitus, Experimental/blood , Male , Nitric Oxide Synthase/antagonists & inhibitors , Oxidation-Reduction , Rats , Rats, WistarABSTRACT
NO-synthase activity, the content of stable products of NO metabolism (nitrites and nitrates) as well as fragmented DNA as biochemical marker of apoptosis have been determined in segmentonuclear neutrophilic granulocytes and mononuclear leukocytes in blood of healthy donors and patients with type 1 diabetes mellitus. It was found that activation of apoptosis in polymorphonuclear and mononuclear blood leukocytes under diabetes mellitus was accompanied by an elevation of NO-synthase activity and the content of stable NO metabolites. This suggests an increase of proapoptotic action of nitric oxide in immunocompetent blood cells under the pathology studied.
