Free Radical Oxidation Processes Research Articles

Free radical oxidation (autoxidation) of alkenones and other lipids in cells of Emiliania huxleyi

Cells of the coccolithophorid Emiliania huxleyi strain CS-57 grown under an atmosphere of air + 0.5% CO 2 showed oxidative damage after 10 days growth with concomitant and major changes to the lipid composition. The fatty acid profile was strongly altered and lacked appreciable amounts of the polyunsaturated fatty acids (PUFA: C 18:5, C 18:3 and C 22:6) typical of healthy cells. Oxidation products of these PUFA could not be detected, but monounsaturated fatty acids proved to be good indicators of oxidative processes. The presence (after NaBH 4-reduction) of a high proportion of 11-hydroxyoctadec- cis-9-enoic and 8-hydroxyoctadec- cis-9-enoic acids showed that the degradation of oleic acid involved mainly free radical oxidation processes (70–75% autoxidation and 20–25% photooxidation). We also detected large amounts of degradation products of the oxidation product 9,10-epoxyoctadecanoic acid including diols, methoxyhydrins and chlorohydrins. These oxidative effects were found in all the lipid classes examined. Products included significant amounts of chlorophyll side-chain autooxidation products Z- and E-3,7,11,15-tetramethylhexadec-3-ene-1,2-diols and Z-and E-3,7,11,15-tetramethylhexadec-2-ene-1,4-diols, while phytyldiol was present in relatively low proportions. Δ 5-3β,7-epimeric unsaturated steroidal diols arising from the autooxidation of the Δ 5 double bond of epi-brassicasterol and minor amounts of Δ 4-3β,6-diols were also detected. Long-chain unsaturated ketone (alkenone) content per cell was much higher in the presence of 0.5% CO 2 likely due to carbon storage under these conditions. The proportions of di- and tri-unsaturated alkenones was relatively stable throughout the growth cycle in the absence of additional CO 2, but not when grown with 0.5% CO 2. The detection of characteristic alkenone autoxidation products in cells grown under these latter conditions allowed us to attribute the significant increase in index observed to the involvement of free radical oxidation processes.

Toxic effect of vepesid on morphology and function of the rat liver

Intravenous injection of antitumor drug vepeside in the maximum tolerated dose (MTD) stimulated free radical oxidation processes in rats. Activities of blood aminotransferases and alkaline phosphatase changed. Morphological study of the liver revealed fatty degeneration, hepatocyte necrosis, and inflammatory infiltration.

Novel n-3 Fatty Acid Oxidation Products Activate Nrf2 by Destabilizing the Association between Keap1 and Cullin3

Consumption of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can mitigate the progression of diseases in which oxidative stress represents a common underlying biochemical process. Nrf2-regulated gene expression regulates detoxification of reactive oxygen species. EPA and DHA were subjected to an in vitro free radical oxidation process that models in vivo conditions. Oxidized n-3 fatty acids reacted directly with the negative regulator of Nrf2, Keap1, initiating Keap1 dissociation with Cullin3, thereby inducing Nrf2-directed gene expression. Liquid chromatography-tandem mass spectrometry analyses of oxidized EPA demonstrated the presence of novel cyclopentenone-containing molecules termed J3-isoprostanes in vitro and in vivo and were shown to induce Nrf2-directed gene expression. These experiments provide a biochemical basis for the hypothesis that formation of J-ring compounds generated from oxidation of EPA and DHA in vivo can reach concentrations high enough to induce Nrf2-based cellular defense systems.

Impact of Postresuscitative Endogenous Intoxication on Lipid Peroxidation Processes in the Experiment

Endogenous intoxication and free radical oxidation were studied in rats after 10-minute clinical death due to systemic circulatory arrest. There were qualitative and quantitative changes in toxic substances throughout a 35-day postresuscitative period, as well as increased free radical oxidation processes in the vital organs (brain, liver, kidneys). At the same time, plasma samples showed inhibited chemiluminescence along with the elevated levels of low and medium molecular-weight substances since medium-weight molecules bound ferrous iron ions that were added to induce luminescence. The chemilu-minescence technique may serve as a rapid method for evaluating the degree of endogenous intoxication.

Impact of Laser Radiation on the Rate of Free Radical Oxidation in Hypovolemic Hypotension and After Reinfusion: Experimental Study

The impact of laser radiation (LR) on the rate of plasma free radical processes during hypotension and after reinfusion was studied in acute experiments on non-inbred albino rats with prior severe hypovolemic hypotension (blood pressure, 25—30 mm Hg) during 60 min. LR used before blood loss was shown to increase total plasma antioxidative activity and to promote the decreased production of lipid peroxidation products during hypotension. Inclusion of LR into a package of resuscitative measures deteriorates free radical oxidative processes. LR may be a promising method for correcting the excessive rate of free radical oxidation after reinfusion at later rehabilitative stages (after recovery of the energetic potential and adaptation mechanisms).

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.

Antioxidant Behaviour of Thia Fatty Acids

Eight thia fatty acids and other sulfides have been studied as inhibitors of autoxidation of arachidonic acid. The inhibitors extend the lag phase of the oxidation, to varying degrees. A carboxyl group in the vicinity of the sulfur reduces the antioxidant activity, while unsaturated sulfides are more effective than their saturated analogues. The results are consistent with the sulfides acting to reduce fatty acid hydroperoxides, which otherwise accumulate during the early stages of reaction and propagate the free-radical oxidation process.

The effect of thyroxine isomers on the processes of free radical oxidation in the subcellular fractions of the rat cerebral cortex

Effective concentrations for D and L thyroxin isomers were determined by the chemiluminescent (CL) method and their effects on free radical oxidation in the mitochondrial and synaptosomal fraction of adult rat cerebral cortex were studied in vitro. A OA DT4 in a model system with riboflavin was 2.2 times higher than L-T4. Effective concentrations for both thyroxin forms were 1$q= = 7.43 x 10~5+/-0.71 M for D-T4 and 15q=15.47 x 10~5+/1.23 M for L-T4. Thyroxin effect on membranous fraction of the brain cortex was studied in vitro using luminol-dependent peroxide CL. In normal concentrations (1 x 108 M) both hormone forms exerted equally intensive antioxidant effect which was more pronounced in the mitochondrial fraction, where CL decreased by 69 and 66%, while in the synaptosomal fraction it decreased only by 45 and 46%. Since D form possesses no hormonal activity, this effect may be due to phenol origin of thyroxin.

Influence of dihydroquercetin on the lipid peroxidation of mice during post-radiation period

The effect of the natural antioxidant dihydroquercetin was examined on the process of free radical oxidation of serum and liver lipids of mice, after a single 4 Gy dose of γ-irradiation. The content of lipid peroxidation products reacting with thiobarbituric acid in irradiated animals receiving oral dihydroquercetin (experimental) for 155 days after irradiation was significantly lower compared with animals receiving irradiation and no antioxidant (controls). The intensity of Fe2+-induced chemiluminescence of liver homogenates of experimental mice was lower by the end of the experiment (p < 0.001) than the chemiluminescence of liver homogenates of both control and intact animals. It is assumed that this was due to the preferential uptake of dihydroquercetin by the liver. Copyright © 1998 John Wiley & Sons, Ltd.

Disorders features of lipid free radical oxidation processes in prepubascent poisoning by thiacetamide

Disorders features of lipid free radical oxidation processes in prepubascent poisoning by thiacetamide

Disorders Features of Lipid Free Radical Oxidation Processes in Prepubescent Poisoning by Thiacetamide

Disorders Features of Lipid Free Radical Oxidation Processes in Prepubescent Poisoning by Thiacetamide

ON THE ORIGIN OF 628 nm FLUORESCENCE IN CERTAIN CHLOROPHYLL PREPARATIONS

Abstract— A fluorescence band at 628 nm seen in certain preparations of chlorophyll on polyethylene particles swollen with tetradecane comes not from an impurity of protochlorophyll in the original chlorophyll, but from a substance like protochlorophyll formed upon adsorption of chlorophyll to the particles. Much of the chlorophyll is grafted to polyethylene in the same particles by a process that does not affect the chromophore. These and other properties peculiar to the particles are tentatively ascribed to a prior free radical oxidation process in the swollen particles.

Oxidative damage in Alzheimer's dementia, and the potential etiopathogenic role of aluminosilicates, microglia and micronutrient interactions.

While evidence implicating free radical oxidative processes in the etiopathogenesis of Alzheimer's dementia is accumulating, the specific cellular and biochemical mechanisms involved remain to be identified. The potential pathogenic role of microglial cells in neurodegenerative processes is indicated by the finding that purified murine microglial cells exposed in vitro to various model aluminosilicate particles stimulate the generation of tissue-injurious free radical reactive oxygen metabolites. Analogous inorganic aluminosilicate deposits have been reported to occur in the core of the characteristic senile plaques found in the brains of Alzheimer disease subjects. The possible modulation of free radical oxidative activity by antioxidant micronutrients and pharmacological agents, provides a rational basis for further preventative and therapeutic clinical investigations.

Influence of the inhibition of free-radical oxidation processes in early postnatal ontogenesis on learning in adult rats

The influence of the neonatal administration of the synthetic antioxidant mexidol on teaching rats an active avoidance conditioned reflex at the age of two months was studied. It was established that the inhibition of free-radical oxidation in the tissues of three to seven day old infant rats subsequently leads to facilitation of the learning process: to a decrease in the latent period of the avoidance reaction by a factor of 4-6, a two-fold increase in the conditioned reflex response, and a decrease in total motoric activity at the stage of the stably developed reaction.

Inhibiting properties of monomethyl ethers of ubiquinols and their mixtures with tocopherols

Ubiquinones and related compounds possess varied biological functions. In particular, it is believed that together with tocopherols, they participate as natural antioxidants in the regulation of chain processes of free-radical oxidation in the tissues of living organisms. It has been established that the reduced form of ubiquinone (ubiquinol) possess high antiradical activity in reactions with perioxide radicals; the activity of the quinoid form is i000 times lower [7, 8].

Fish oils inhibit endothelial cell production of platelet-derived growth factor-like protein.

Diets rich in fish and fish oils are associated with a reduced risk of cardiovascular disease and atherosclerosis. The interaction of a commercial fish oil extract (MaxEPA) with vascular endothelial cells (ECs) was studied as a possible mechanism for this protective effect. MaxEPA almost completely inhibited EC production of platelet-derived growth factor-like protein (PDGFc) while other lipids had a lesser effect or no effect. Overall protein synthesis was not reduced, nor was the inhibition due to defective secretion or increased degradation of the growth factor. Antioxidants suppressed the inhibitory activity of MaxEPA indicating that free radical oxidative processes were required for the inhibition. These results suggest that fish oils may suppress intimal smooth muscle cell proliferation by decreasing the production of EC-derived paracrine growth factors. This inhibitory process represents a possible molecular mechanism for the antiatherosclerotic action of marine lipids.

Role of free-radical oxidation in the pathology of newborns and infants

The processes of free-radical oxidation of lipids are considered to be the fundamental molecular mechanism of biological membrane damage. At the present stage, significant data have been accumulated on the activity of lipid peroxidation processes in acute pathology in children.

Participation of the endothelium in the development of the atherosclerotic plaque

In the past decade, initiated by the response-to-injury hypothesis of Ross and Glomset, the endothelium has been implicated in atherogenesis but as a passive participant--more involved through its absence than its presence. The hypothesis stated that endothelial desquamation due to an undefined injury led to platelet adhesion to the exposed basement membrane, and infiltration of serum lipoproteins. The subsequent release from the platelet alpha-granule of a potent smooth muscle cell mitogen and chemoattractant--the platelet-derived growth factor (PDGF)--was postulated to cause the intimal proliferative response that is known to be important in atherosclerotic plaque development. Recent evidence from several laboratories indicates that the endothelium has the potential to play a more active role in plaque development than simply contributing to pathological sequelae resulting from the loss of the nonthrombogenic surface provided by the endothelium. First, the endothelial cell (EC) is the site of attachment, and possibly activation, of blood-borne monocytes which enter the vessel wall as an early event in experimental atherogenesis. We have obtained in vitro evidence that the expression of monocyte binding sites on the surface of EC is a regulatable process and that increased EC turnover and certain exogenous agents acting on EC cause increased monocyte adhesion. Similar events may be responsible for focal adhesion of monocytes to the endothelium in vivo following hypercholesterolemia. Secondly, EC in culture are capable of chemically modifying low density lipoprotein (LDL) by a free radical oxidation process that renders the LDL toxic to proliferating cells and recognizable to the scavenger receptor of monocyte-derived macrophages. Thus, by oxidation of LDL, the EC have the potential to play an active role both in the formation of lipid-laden foam cells and in the accumulation of necrotic tissue which are hallmarks of the atherosclerotic lesion. Thirdly, cultured EC have been recently shown to secrete multiple mitogens for cultured smooth muscle cells. One of these mitogens appears to be closely related, if not identical, to PDGF using the criteria of receptor binding and biochemical and immunological similarity. Production of growth factors by EC is a regulatable process that is stimulated by exogenous agents such as endotoxin and phorbol esters which cause severe injury to cultured EC. Such a regulatory mechanism may participate in the in vivo proliferation of vascular SMC during the atherosclerotic process.(ABSTRACT TRUNCATED AT 400 WORDS)

Cell surface and cell division.

A mathematical model of the regulation of cell division is suggested. The model is based on the hypothesis that the process giving rhythm to cell division is located in the cell membrane: i.e., the process of free-radical oxidation of membrane lipids. Much depends on the physical state of the membrane. In the membrane, phase transitions take place because of the changes in lipid composition. These transitions differ in normal and tumor cells: in normal cells they are sharp and hysteretic owing to the presence of a framework (membrane skeleton) on the surface of the membrane, while in tumor cells the integrity of the surface is violated so that the transitions are smooth. This model makes it possible to explain differences in the regulation of normal and cancer cell proliferation. Within the limits of the model, such phenomena as density dependent inhibition of growth, reverse transformation, influence of cyclic AMP and ions of Ca2+ on the cell cycle, the actions of serum and of proteases on the cycle, and so on, are explained. A rational scheme for the appearance of the selective damage found in tumor cells is proposed.

Effect of ischemic anoxia and barbiturate anesthesia on free radical oxidation of mitochondrial phospholipids

The mitochondrial fraction obtained from brains of animals submitted to ischemia shows a decrease of phospholipid level, especially plasmalogens in the fraction of ethanolamine phospholipids and choline phospholipids. THere appears simultaneously an increase of free radical oxidation processes of unsaturated fatty acids from these phospholipids. The peroxidation processes of mitochondrial lipids are stimulated by calcium ions and, to a smaller extent, by magnesium ions. Barbiturate anesthesia inhibits the peroxidation of fatty acids and increases the antioxidant abilities of the nervous tissue. Nembutal added in vitro remains without effect on the above processes. The effect of acetylcholine and the antioxidant ability of nervous tissue under barbiturate anesthesia with respect to ischemia are discussed.