Information on the thesis

The dissertation is devoted to the study of the effect of agmatine on the aggregation
and migration abilities of peripheral blood leukocytes both in control rats and those with
experimental diabetes mellitus (EDM) by determining changes in oxidative stress indices
and polymerization-depolymerization processes of actin filaments.
The administration of agmatine prevents the development of oxidative stress in rat
leukocytes under streptozotocin-induced diabetes, suppresses the formation of active
forms of oxygen, reduces the intensity of lipid peroxidation processes and the content of
advanced oxidation protein products in plasma, and also increases the activity of the
antioxidant system key enzymes (superoxide dismutase, catalase, glutathione peroxidase,
glutathione reductase).
After the injection of agmatine to both healthy and diabetic animals the enhancement
of aggregation properties of peripheral blood leukocytes as were observed, which may be
explained by the direct action of agmatine either on the state of surface glycoconjugates of
leukocyte membrane or on the activity of enzymes which form the structure of
carbohydrate determinants of adhesive molecules of these cells. The directed action of
agmatine was also kept under the conditions of EDM. Thus it may be assumed that the
administration of agmatine to animals with diabetes causes an increase in the affinity of
WGA lectin binding to its complementary ligands due to an increase in the number of
sialoglicoconjugates and residues of N-acetyl-D-glucosamine in the surface glycans of
leukocytes.
The initial level of polymerized actin in rat peripheral blood leukocytes of all the four
groups was estimated by the level of fluorescence of phalloidine, which binds F-actin in
the ratio of 1: 1 without binding G-actin. The digitized results of the signal intensity of
fluorescence microscopy were expressed in conditional units. It was found that the level of
F-actin in leukocytes under EDМ was significantly higher compared to the control, which
indicates their pre-activated condition, the violation of depolymerization processes,
changes in structural and functional properties of the cells thus decreasing their migration
capacity under diabetes mellitus.
After the injection of agmatine to both the control group of rats and under conditions
of streptotrozotocin-induced diabetes, a decrease in the level of polymerized actin was
observed. Such results in animals with EDМ following the injection of the studied
polyamine may be attributed to the “removal” of the pre-activation state of cells, the
intensification of actin polymerization-depolymerization, which was recorded as an
increase in the long actin filaments content, thus increasing the migration capacity of cells.
In leukocytes of animals with EDМ against a background of agmatine injection, the
transduction of the lectin-induced signal via sialoglicoconjugates and the dynamics of
quantitative redistribution of the content of actin fractions indicates that this polyamine
helps restore and maintain the functional response of leukocytes to activation signals.
Agmatine prevents the development of oxidative-nitrative stress in rat leukocytes in
conditions of streptotrozine-induced diabetes by inhibition NO synthase, decreasing NO
overproduction in leukocytes, reducing the intensity of lipid peroxidation processes, and
also increasing the activity of key enzymes of antioxidant defense. Agmatin exerts
hypoglycemic and antioxidant effects maintaining oxygen and nitrogen active forms
concentrations within the limits of the physiological norm. This contributes to the
restoration of the balance between the processes of polymerization and depolymerization
of actin in blood leukocytes. The increase in the content of the fraction of long filaments
of leukocytes’ cytoskeleton of animals with EDM confirms this effect of agmatine. The
investigation of mechanisms underlying agmatine’s influence on the aggregation and
migration abilities of blood leukocytes under diabetes mellitus is a high pressing priority
since the obtained results may contribute to the development of new approaches to the
development of drugs with hypoglycemic, antioxidant and immunomodulatory effects.
Key words: experimental diabetes mellitus, leukocytes, agmatine, aggregation,
migration, antioxidant system, cytoskeleton, actin.