Oxidative stress in the molecular mechanism of pathogenesis at different diseased states of organism in clinics and experiment.
According to modern images and results of our observations the oxidative stress (OS) is a non-specific though certain component of pathogenesis at numerous diseased states of organism having in the basis the thoroughness of pathogenic disturbances of phospholipids (PL) metabolism and processes of their free radical oxidation (FRO), which takes place in the membrane formations of as the whole cell, as well as the mitochondrial and microsomal fractions (MCF and MSF) of the white rat brain, liver mitochondria, lung shadows, at the same time erythrocyte and lymphocyte shadows at brain acute edema, ischemia, reperfusion and desympathization, infarction of myocardium, tuberculosis of lungs, diabetes, Familial Mediterranean Fever (FMF), intoxications under halothane anaesthesia (HA) and with micotoxin zearalenon. The regularities observed promote to understand from the point of view of modern approaches the molecular mechanisms of initiation, development and generalization of factors for OS formation under pathologic conditions. It is more obvious at zearalenon intoxication with intensification of lipids FRO processes and failures in PL-PL ratio phenomena. The lymphocytes membranes of the white rats spleen subjected OS induced by zearalenon intoxication permit us conclude that the general immune status of the organism decreases. It is generally peculiar to the states under conditions of generalized intoxication. The observed increase of phospholipase A(2) activity induces the release of high concentrations of lysophosphatidylcholines (LPC) and non-etherified fatty acids (NEFA) of polyenic range with prevail of arachidonic acid as a pathogenic factor, namely, at modelling brain acute edema by tetraethylolovo to white rats. Formation of the above mentioned disturbances to some extent depends on hydrophobic properties of toxins, particularly, zearalenon. The latter gives certain tropism to dopamine-beta-monooxygenase (DBM), and ability to stimulate functional activity of the enzyme. Striking haemolytic properties of phospholipase A(2) induced by existence of LPC and NEFA high concentrations, and products of their peroxidation, promote elimination of separate protein fractions of erythrocyte membranes (EM) responsible for OS formation and decrease of erythrocytes resistance to peroxide hemolysis. Increase of DBM activity under the effect of relatively moderate doses of zearalenon (1-15 microg/ml) is accompanied with extra intensification of catecholamine synthesizing function of the organism with lethal result. Data of publications represented testify exceptional efficiency of sodium thiosulfate (STS) as a powerful synergist for endogenous factors of antioxidant effect, particularly alpha-tocopherol (alpha-T), which is the main component for the system of cell antiradical defence. Detoxicating effect of STS can be demonstrated indeed on the example of zearalenon intoxication during the first two hours with the reduction of metabolism disturbances of PL and products of its peroxidation. Comparative evaluation of molecular mechanisms of STS normalizing effect as a supplier for hydrogen and sulphur ions, as well as an effective synergist for alpha-T on the level of various formations of the live cell in compare with the effects of alpha-T and ubiquinone, allowed to make a special accent on the role of STS in interaction with energy-dependent enzymatic systems of cell antiradical defence, as well as accumulation and transformation of energy on the level of mitochondrial membranes. The results obtained by us confirm a number of clinical experimental observations, which demonstrate treatment and prophylactic role of STS at different pathologic states of the organism. STS protectory role at toxic injuries of the organism is higher at its preliminary introduction to the organism before modelling of the studied diseased states, especially at zearalenon and halothane (H) intoxication (in the last case before HA). These data serve a sound affirmation for protectory function of STS, detailed revelation of molecular properties of pathogenesis of the studied intoxication to which a part of our clinical and experimental studies at present is devoted.
Karageuzyan
Konstantin G
KG
Institute of Molecular Biology, National Academy of Sciences of the Republic of Armenia, 7, Hasratyan Str., Yerevan 375014, Republic of Armenia. konstant@mb.sci.am
D000769:Anesthesia, Inhalation / Q000009:adverse effects; D018685:Anesthetics, Inhalation / Q000009:adverse effects; D000818:Animals; D016718:Arachidonic Acid / Q000502:physiology; D001923:Brain Chemistry; D006221:Halothane / Q000009:adverse effects; D006801:Humans; D020104:Immunophilins / Q000502:physiology; D007249:Inflammation / Q000503:physiopathology* / Q000532:radiotherapy; D007259:Infrared Rays; D007834:Lasers; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D051381:Rats
D018685:Anesthetics, Inhalation; D016718:Arachidonic Acid; D020104:Immunophilins; D006221:Halothane