Information on the thesis

The  thesis  is  devoted  to  the  search  of  approaches  of  pharmacological  correction  of
alcohol-induced  oxidative  and  nitrosative  stress  in  platelets  and  erythrocytes  of  rat  blood 20

through the simulation of various levels of NO concentrations and its stable products (NO 2
– ,
NO 3
– ) under alcohol intoxication (AI).
The development of oxidative and nitrosative stress under the studied pathology is the
main cause of the change in structural and functional state of platelets and erythrocytes.
Strengthening of free-radical processes causes the development of oxidative stress in
blood cells under alcoholic intoxication (AI). At the same time, the change of the ratio of
activity  of  isoforms  of  NO-synthase  due  to  inhibition  of  the  activity  of  endothelial
NO-synthase and increase in the activity of inducible NO-synthase causes the development of
nitrosative  stress  under  this  pathology.  NO  overproduction  by  inducible  NO-synthase  and
increase of its pool due to nitrite reductase activity of deoxyhemoglobin under AI leads to a
switching of NO function from physiological regulatory to cytotoxic one.
The development of oxidative-nitrosative stress under AI was reflected in the change of
the cytomorphological characteristic of the studied cells. Under the alcohol intoxication, the
effectiveness of erythropoiesis is disturbed, what is manifested in the increased population of
the  physiologically  old  erythrocytes  on  the  background  of  reduction  of  the  total  number
of cells.
It  was  shown  that  the  consumption  of  the  L-arginine  under  AI  contributes  to  the
restoration of the number of functional red blood cells to normal values.
The effect of ethanol and its metabolites evokes the change in the shape of erythrocytes
and affects the surface structure of the receptor apparatus of their membranes. Under AI the
content  of  lipid-  and  protein-bound  sialic  acids  in  the  composition  of  the  surface  glico-
conjugates of erythrocyte membranes is reduced. It was shown that L-arginine consumption
by the alcoholised rats normalizes the content of membrane-bound sialic acids, accompanied
by  an  increase  of  the  indicators  of  alcian  induced  aggregation  of  erythrocytes,  namely  the
restoration of their functional state.
Under AI, a reduction in the number of platelets in the peripheral blood of rats was
revealed. In these circumstances an ultrathin organization of platelets is impaired, which is
reflected in the change in their aggregation ability. Evaluation of the platelet aggregation by
several  parameters  allowed  assessing  their  state  and  sensitivity  to  the  action  of  the
aggregation  agonist  (ADP)  in  the  peripheral  blood  under  AI  and  confirmed  the  correcting
effect of L-arginine.
Thus, it has been found for the first time that consumption of L-arginine prevents the
development of oxidative and nitrosative stress in erythrocytes and platelets of the peripheral
blood of rats under AIand has cytoprotective effect under this pathology.
Key  words:  alcohol  intoxication,  platelets,  erythrocytes,  hemoglobin,  L-arginine,
methyl ester Nω-nitro-L-arginine, NO-synthase, sialic acids.