Synthetic Antioxidants and Its Effects in Ultra Low Concentrations, Probability of Cardio Protection by Membrane Stabilization-Juniper Publishers
JUNIPER PUBLISHERS-OPEN ACCESS JOURNAL OF CARDIOLOGY & CARDIOVASCULAR THERAPY
Oxygen-Sensing Mechanism
Oxygen-sensing mechanisms are one of the most
important for cell and tissue homeostasis, as well as to adapt to the
chronic low-oxygen condition, but intensive production of reactive
oxygen species (ROS) can cause cell destruction. Endogenous antioxidant
system protects from ROS overproduction, exogenous antioxidants in ultra
low concentrations have protective effects too [1]. Detection of
ability of biologically active substances (BAS) to modify live systems
in ultra low concentration (10-22-10-14М), is one of the most impressing
investments of last decades [2,3]. The specificities of influence of
ultra low doses (ULD) of biologically active substances is complex and
polymodal dependence of effect on dose; kinetic paradoxes; dependence of
reaction on initial characteristics of biological object;
«stratification» of effect (there are no effect in average doses, effect
present only in 10-1-10-3M and 10-10-10-22M); increase in sensitivity
of biological objects after ULD action to influence of other physical
and chemical factors [3].
Mechanisms of these phenomena are actively
investigated. It is a fact, that limitation of the sizes of the some
substance and ULD leads to change of its physical and chemical
characteristic such as charge, magnetization and demagnetizing, the
phenomena of transfer of heat, conditions for phase and structural
transformations; transmission and reflex of light spectrum and etc. Thus
all fundamental characteristics of substance are changed: lattice
parameters, an electronic spectrum, energy of electron detachment from
an external energetic membrane, temperature of fusion and etc. Forces of
an attraction and aspiration to lower free energy create preconditions
for self-organizing and self-assemblage of ultra small objects and
structures, and the nature widely uses with it, especially in biological
objects [4]. It has been shown, that at ultralow concentration the
specific molecules of substancecan form supramolecular nanodimensional
particles, whichcan be considered as hydrophilic surfaces, and a target
of their action in biological objects can be as membrane structures.
Natural and synthetic antioxidants concern that type of agents which
possess this ability [4]. Water soluble synthetic antioxidant Phenozan
(space labored phenols group) has been synthesized in Institute chemical
physicists (Russia). It is strong antioxidant influencing on structure
and functions of membranes. Biologically significant targets of Phenozan
are micro domains of liposome, fragments of a cellular membrane,
superficial cellular receptors and cellular organelle, also system of
signal transduction, reparation and apoptosis of cells. Phenozan in
concentration 10-14М/kg increased life expectancy in leucosis mouses
(Erohin A., 2008), Phenozan can stabilize DNA-molecule by decreasing of
its breaks after radiation, so it can be used as radio protector.
Phenozan in ULD have ability to block purines receptors (PY2) and
calcium channels (CRAC), so it have influence to the signal transduction
system of the cell [2]. Phenozan can modify activity of some
enzymes-membrane-binded and soluble acetyl cholinesterase, proteinkinase
C, lactatdehydrogenase (LDG), superoxiddismutase (SOD),
glutationperoxidase. Mitochondrial enzymes are more sensitive to
Phenozan, vs cytoplasm enzymes [4] Phenozan can modify activity of LDG
in brain microsomes in vivo, increase activity of
glutation-S-transferase, decrease NO-production in macrophages [5].
Phenozan leads activation of anti-apoptotic proteins bcl-2 and p53 [3].
We have discovered ability of Phenozan to decrease oxidation of brain
phospholipids in dose 10-16М/kg in newborn rats after experimental
chronic fetal hypoxia [6]. Phenozan in ULD leads to statistically
significant (p<0,01) decrease of MDA level and increase of the ROS
scavenger enzymes in a brain, peripheral blood and in microsomal and
mitochondrial fractions of the liver at this experiment. During
treatment with 10 enteral doses of Phenozan (10-16М/kg) in
brain tissues observed the normalization of SOD activities
(on 5th day), katalase activities (on 8th day), level of MDA (on
10th day). We suppose that treatment with ULD of Phenozan
cause decreasing of ROS generation in brain tissues at critical
periods of its development in newborn rats [6]. Significance of
this data support that ultra low doses of Phenozan can be less
invasive and effective in the treatment of chronic intrauterine
hypoxia and suggest the directions for further research of its
membranoprotective effects in cardiology.
Cytoprotective and cardioprotective effect was founded
at serin proteases inhibitor Aprotinin in a prospective,
randomized, double-blind, placebo-controlled trial: low-dose
postoperative aprotinin reduces mediastinal drainage and
blood product use in patients undergoing primary coronary
artery bypass grafting, in ULD Aprotinin causes modulation of
antithrombotic enzymes and leads decreasing of transfusional
complications [7]. Oxidative stress and apoptosis are major
mechanisms of cell damage at hypoxia, which is common
at cardiovascular diseases [8]. So, ULD of antioxidants
have approved positive membrane stabilizing effects,
they are potential cyto-protectors, which may be tried in
cardioprotection for cardiomyocytes membrane stabilization.
(Memories of my teachers – academician U.K. Ibragimov
and E.B.Burlakova is denoted).
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