Marakushyn D. Pathophysiological mechanisms in the development of structural-metabolic and functional disorders under the effect of oxyethylated nonylphenols and their derivatives on the organism

The thesis discovers pathophysiological mechanisms in the development of structural-metabolic and functional disorders under the effect of oxyethylated nonylphenols (EONP) and their derivatives on the organism. It has been revealed that the main link in the effect of EONP and their derivatives on the organism consists in the development of oxidative stress, which causes disorders in experimental animals, first of all in the structural-functional state of their cellular membranes (particularly changes in the phospholipid composition with an increased number of phospholipid lysoforms, and in the fluidity and permeability of blood cell membranes) as well as in redox homeostasis (cancellation of triggering of redox-sensitive signalling systems and neutralization of the messenger function of reactive oxygen species, a significant tension of adaptive and compensatory mechanisms, unbalance of homeostasis supporting systems: immune, nervous and endocrine. But it is necessary to consider here the chemical nature and physiochemical properties (presence of hydrophobic and hydrophilic groups, capacity for chemical transformations with formation of biologically active compounds, etc.) of the studied substances, which results in their ability to have a direct effect on cellular membranes. Therefore the principal effect of the action of EONP and their derivatives in the organism is membranotoxic; the latter is realized through a possible direct contact of substances with cellular membranes as well as indirectly through initiation and intensification of free-radical processes. It has been proved that supplementation of the standard food ration of experimental animals with ascorbic acid, alpha-tocopherol, beta-carotene and a polymicroelement preparation (a composition of essential microelements - zinc, iron, manganese, copper, chromium and cobalt - with N-2,3-dimethylphenylanthranilic acid and oxygen-containing salts of ultramicroelements - selenium, vanadium and molybdenum) results in a significant improvement of the dynamics of changes in key indicators of oxidative homeostasis disorders, a less marked development of oxidative stress, a longer increase of adaptive responses and a delay in the shift of the oxidative-antioxidative balance towards oxidants.