Influence of the characteristics of lipids on the regulation of biochemical processes in animal liver and blood

It has been established experimentally that the character and the scale of interrelations between various parameters of the phospholipid composition and their group-average values depend significantly on the characteristics of lipids (the antioxidative activity, quantity of peroxides, and antiperoxide activity) of animal liver and blood erythrocytes. It was shown that a single injection of low-toxicity Tween 80 and acetone at low doses modifies the intensity of lipid peroxidation in the liver and changes the physicochemical properties of lipids, and the interrelations between the parameters that are coordinated in norm, thereby causing the disturbance of biochemical functions of the liver.     

The regulation of the oxidative processes in the tissues of Muridae like rodents caught in the Chernobyl accident zone

The results of the investigations of the radioactive contamination consequences on the lipid peroxidation (LPO) processes in organs and tissues of wild rodents which were caught in the Chernobyl NPP accident 30-km zone during 1986-1993 are generalized. The behaviors of the technogenic contamination effect on dynamic of changes of the LPO physico-chemical regulatory system parameters and the generalized parameters of the phospholipid composition in organs of the different radioresistance wild rodents are revealed in dependence on the radioactive contamination level and the duration of the radiation factor exposure. Different sensitivity of the LPO regulatory system parameters in wild rodent tissues to the radioactive contamination of their environment and the unequal ability to normalization of the antioxidant status and the energy exchange in tissues result in the change of the scale and character of interrelations between the reciprocal parameters in norm and have an influence on the development of qualitatively new subpopulations of wild rodents due to the transition of the cell regulatory system to the another level of the function.     

Participation of the lipid peroxidation processes in the adaptation mechanism of Muridae like rodents to the radioactive contamination of the Chernobyl NPP zone

Results of the comparative analysis of the complex investigation of rodent population state caught at areas with different levels of contamination in the accident zone of the Chernobyl NPP during 1986-1993 and 2007, at areas with a practically normal radiation background in the neighborhood of the Kiev City in 1993 and at areas with the normal and increased radiation background in Ukhta region of Komi Republic in 1993-2008 are presented. It is shown that the absence of the linear dependence in changes of the lipid peroxidation (LPO) regulatory system parameters in rodent tissues on the dose of the external gamma-radiation at areas of their trap persists for a long time. Different ability to normalization of the studied indices and nonlinearity of their dose dependences allow us to suggest that changes of the scale and direction of interrelations between the reciprocal parameters of the LPO regulatory system in norm in tissues of rodents which were caught in the accident zone and at areas with an increased radiation background should be the information signal determining selection of the strategy of adaptation to the chronic radiation factor action.     

A new approach to assessment of biological consequences of exposure to low-dose radiation

A high sensitivity of characteristics of the lipid metabolism in erythrocytes to exposure to low doses of gamma- and X-rays was found; the changes in lipid peroxidation (LPO) of blood components were persistent, which substantially influenced the development of biological consequences of low doses of radiation. The effect of low doses of radiation on the interrelation between the LPO intensity in blood plasma and the lymphocyte DNA structural integrity or the cell-free DNA content in animal blood plasma was found. Different sensitivity of the examined parameters (neither normalization nor linear dependence on a dose rate was found) implies the transition of the LPO regulatory system to another level of functioning due to scale changes of interrelations between the examined parameters under influence of low doses of radiation. These findings make possible to assess biological consequences of radiation factor for animal groups by the scale changes of interrelations between the examined characteristics in blood plasma.     

Physiological phenotypes of immune resistance and their significance in assessment of health level

The health status was assessed in virtually healthy residents of the Far East south by the parameters describing the organism’s resistance on the integration level of the immune system and systems of lipid peroxidation and antioxidant protection (LPO-AOP). New data on the immunophysiological mechanisms in the development of the regional adaptive norm of immune system and LPO-AOP of cell membranes are presented. System analysis showed that the immunophysiological norm in the population was presented by eight main functional phenotypes of immune resistance: resistant, T-hyposuppressor, T-helper, resistant and nonresistant T-suppressor, compensated and subcompensated hyporesistant, and deficient. The prospects of immune resistance phenotype determination for the assessment of individual and population health level are discussed. The concept presented is a theoretical base for a new approach to the health assessment which deals with diagnostics and the early prevention of premorbid disorders considering the regional dynamic stereotype of physiological functions.     

Interconnection of parameters of regulation system of lipid peroxidation and of morphophysiological parameters of mouse liver

A complex analysis of seasonal fluctuations of the mean group parameters of the system of regulation of lipid peroxidation has been performed in liver of Balb/c mice. Association of lipid characteristics and morphophysiological parameters is studied in the Balb/c mouse liver. An inter-connection is revealed between the liver index and the amount of lysoforms of phospholipids, the scale and character of the interconnection differing essentially depending on proportion of phos-phatidylcholine in mouse liver phospholipids.     

Influence of the antioxidant status on the characteristics of lipids in tissues of animals after acute irradiation with sublethal doses

The effect of the acute exposure to sublethal doses of X-rays on the interrelation between parameters of the lipid peroxidation regulatory system (lipid antioxidative activity, AOA; peroxide amount, lipid composition) was studied in liver, spleen and blood erythrocytes of CBA and SHK mice and rats within 1 month after irradiation. The reverse correlation between the lipid AOA values and the initial peroxide amount in lipids of the CBA mice spleen was found. The coefficient of the linear regression of this correlation for the exposed mice was 1.8-fold higher as compared with control. The correlative dependence between the ratio of the sums of the more readily to more poorly oxidizable phospholipid and the ratio of phosphatidyl choline to phosphatidyl ethanolamine content in phospholipids of liver and blood erythrocytes was revealed. The direction (the phospholipids of the rat liver) or the value of the linear regression coefficient of that correlation were different for groups of the exposed and control animals, especially in the blood erythrocytes. Thus, the different sensitivity of examined characteristics of lipids and the possibility of their normalization in the dependence on the lipid AOA value cause the conversion of the lipid peroxidation regulatory system in organs and blood erythrocytes of the exposed animals to the other scale of the functioning.     

Changes in the physico-chemical characteristics of mouse liver lipids after administration of a mixture of unsaturated fatty acids

The effects of a mixture of unsaturated fatty acids (UFA) on changes in the lipid oxidation substrate, a system of natural antioxidants and the functioning of a system controlling lipid peroxidation were studied. It was shown that arachidonate induces the incorporation of fatty acids into individual lipid fractions and the dilution of lipids by UFA esters, as a result of which the relative amount of natural antioxidants diminishes. Under these conditions, the oxidative capacity of lipids decreases, which manifests itself in a reduction of the rate of natural antioxidants utilization and an increase in their number. It was shown that purposeful modification of the lipid substrate does not interfere with the interaction between individual parameters of the system controlling lipid peroxidation.     

Morphofunctional and biochemical properties of erythrocytes in early postnatal ontogenesis in rats in norm and after prenatal stress

Morphofunctional and biochemical properties of erythrocyte membrane were investigated in early postnatal ontogenesis in rats in norm and after prenatal immobilization stress. The transient decrease of erythrocyte membranes stability was revealed in the control rats. The ability to erythrocyte transformation and the concentration of lipid peroxidation products are increased. It has been shown by an increase of percentage discocytes and lower lipid peroxidation level that the erythrocyte membrane of the rats after prenatal stress is more stable.     

Phosphorescent analysis of lipid peroxidation products in isolated human erythrocyte membranes

The room temperature phosphorescence of lipid peroxidation products in the composition of isolated human erythrocyte membranes was registered, and its kinetic parameters were determined. The excitation and emission spectra of phosphorescence of lipid peroxidation products in the composition of erythrocyte membranes at 0 degree C measured. The nature of lipid peroxidation products possessing the phosphorescencing capacity was discussed. Based on the analysis of temperature dependences of the intensity and lifetimes of phosphorescence of lipid peroxidation products in the range -2 divided by 26 degrees C, it is concluded that the deactivation of excited triplet states of lipid chromophores was realized by the dynamic type.     

Reliability of autoregulatory mechanisms of biosystems as affected by ionizing radiation

Reliability of biosystems in processes of adaptation and homeostasis after whole-body irradiation of rats with different doses was determined in terms of the stochastic process theory developed for the autoregulatory systems with random parameters. Fluctuations in the rate of spontaneous chemiluminescence of blood serum and accumulation of lipid peroxidation products by erythrocyte membranes of rat blood were taken as the initial material. The analysis of fluctuations of peculiar parameters permitted to predict the adaptability of the system and to make timely corrections.     

The parameters of antioxidant status of tissues in the offspring of tundra vole (Microtus oeconomus Pall.) inhabiting areas with increased natural radioactivity

The parameters of the lipid peroxidation regulatory system (the antioxidative and antiperoxidant activities, the peroxide content, the lipid peroxidation intensity) in the tissues and the activities of the antioxidative defence enzymes (the peroxidase activity in blood, the superoxide dismutase activity in the blood erythrocytes) are studied in progeny of tundra vole which are reproduced from parent inhabiting areas with different radioecological environment during a long time. The progeny had the preservation of the changed antioxidant status. The scale of the changing of the investigating parameters depend on the state of radionucleoids contamination of areas where tundra voles are caught, sex of rodents, the content of antioxidants in lipids of tissues of parents.     

Phylo- and ontogenic characteristics of lipid peroxidation in the retina of vertebrates

Phylo- and ontogenetic aspects of lipid peroxidation and antioxidative enzyme system in the retina of vertebrates were studied. It was established that both the intensity of lipid peroxidation and the activity of glutathione peroxidase in the retina of different vertebrate animals (carp, frog, tortoise, pigeon, rabbit) considerably diminished with evolution. The differences in the intensity of lipid peroxidation and the activity of glutathione peroxidase between dark- and light-adapted retinas also decreased depending on the level of the development. The activity of glutathione peroxidase in the retina of chick embryos was found only at the end of the incubation period.     

Breath alkanes as a marker of oxidative stress in different clinical conditions

We assessed oxidative stress in three different clinical conditions: smoking, human immunodeficiency virus (HIV) infection, and inflammatory bowel disease, using breath alkane output and other lipid peroxidation parameters such as plasma lipid peroxides (LPO) and malondialdehyde (MDA). Antioxidant micronutrients such as selenium, vitamin E, C, beta-carotene and carotenoids were also measured. Lipid peroxidation was significantly higher and antioxidant vitamins significantly lower in smokers compared to nonsmokers. Beta-carotene or vitamin E supplementation significantly reduced lipid peroxidation in that population. However, vitamin C supplementation had no effect. In HIV-infected subjects, lipid peroxidation parameters were also elevated and antioxidant vitamins reduced compared to seronegative controls. Vitamin E and C supplementation resulted in a significant decrease in lipid peroxidation with a trend toward a reduction in viral load. In patients with inflammatory bowel disease, breath alkane output was also significantly elevated when compared to healthy controls. A trial with vitamin E and C is underway. In conclusion, breath alkane output, plasma LPO and MDA are elevated in certain clinical conditions such as smoking, HIV infection, and inflammatory bowel disease. This is associated with lower levels of antioxidant micronutrients. Supplementation with antioxidant vitamins significantly reduced these lipid peroxidation parameters. The results suggest that these measures are good markers for lipid peroxidation.     

Role of the liver in the regulation of circadian rhythm of blood iron in rats]

In experiments with Wistar rats there was discovered statistically significant circadian rhythm of serum iron concentration reaching its maximum in the evening, minimum--early in the morning, and having an amplitude of at least 20% of the mesor. The reciprocal interrelations between circadian cycles of iron content in blood and liver were also found. The synchronization of blood iron level with lipid peroxidation products in membranous liver structures, as well as serum alanine aminotransferase activity, and their inversion with respect to the circadian rhythms of liver RES absorption ability and liver iron content are considered to be a proof of liver participation in regulation of iron exchange temporal organization in rats.     

The influence of NADPH-dependent lipid peroxidation on the progesterone biosynthesis in human placental mitochondria.

In an in vitro system consisting of human term placental mitochondria and an NADPH-generating system plus Fe2+, significant lipid peroxidation was observed along with a concomitant inhibition of progesterone biosynthesis. This inhibition could be markedly blocked by Mn2+, superoxide dismutase and dimethylfuran, inhibitors of NADPH-dependent lipid peroxidation. In addition, it has been found that malondialdehyde formation is accompanied by a corresponding decrease in placental mitochondrial cytochrome P-450 content. Inhibitors of lipid peroxidation also prevent the loss of cytochrome P-450, further demonstrating a direct relationship between NADPH-dependent lipid peroxidation and degradation of cytochrome P-450 in cell-free systems. These measurements provide the first evidence that the inhibition of progesterone biosynthesis by a NADPH-dependent lipid peroxidation in placental mitochondria is a consequence of cytochrome P-450 degradation due to lipid peroxidation.     

NADPH-dependent lipid peroxidation capacity in unfixed tissue sections: characterization of the pro-oxidizing conditions and optimization of the histochemical detection

Summary Factors which influence the iron-stimulated lipid peroxidation in rat liver have been studied by incubating unfixed cryostat sections with a pro-oxidant system and using an optimized histochemical detection method for lipid peroxidation products with 3-hydroxy-2-naphthoic acid hydrazide and Fast Blue B. We used a method that was slightly different from the one described previously. The final reaction product was exclusively localized in the cytoplasm of liver parenchymal cells with a homogeneous distribution within the liver lobule. The absorbance maximum, as measured cytophotometrically, was found to be 550 nm. Maximum lipid peroxidation was observed when the pro-oxidant system contained 0.2 mm NADPH, 1 mm ADP and 15 μm FeCl₂. Some reaction product was found when NADPH was omitted. Iron concentrations higher than 180 μm prevented the formation of lipid peroxidation products in certain areas of the sections, whereas ADP concentrations higher than 1 mm inhibited the reaction in the whole section. A pH dependency was also observed, with the highest lipid peroxidation at pH 7.2. Optimum lipid peroxidation was induced by incubating for 30 min at 37°C with the pro-oxidant system. A linear relationship was found between the thickness of the sections (up to 20 μm) and the amount of lipid peroxidation products. The addition of scavengers of O2- (superoxide dismutase), hydrogen peroxide (catalase) and OH · (mannitol) to the first step medium did not affect the amount of final reaction product. These findings appear to confirm the hypothesis proposed for events occurring in isolated microsomes, leading to the formation of hydroperoxides and ultimately lipid peroxidation-derived carbonyls. The present method is a useful tool for studying the capacity of lipid peroxidation in tissues under different (patho)physiological conditions.     

The effect of cyclooxygenase inhibition on the indices of the thrombocyte-vascular link in hemostasis and on the free-radical processes of lipid oxidation in experimental Salmonella intoxication]

Injection of Salmonella typhimurium endotoxin to the laboratory animals (rabbits) in dose of 1 mg/ml (LD84) induces the particular changes in the thrombocyte vessels system of hemostasis: decrease of aggregatory ability of thrombocytes, increase of thromboxane A2 and prostacyclin activation of lipid peroxidation process. Use of indomethacin--the cyclooxygenase inhibitor--leads to less progressive alterations of the studied parameters of the thrombocyte vessels hemostasis and lipid peroxidation processes.     

Increased Reactive Oxygen Species Formation and Oxidative Stress in Rheumatoid Arthritis

BackgroundRheumatoid arthritis (RA) is an autoimmune inflammatory disorder. Highly reactive oxygen free radicals are believed to be involved in the pathogenesis of the disease. In this study, RA patients were sub-grouped depending upon the presence or absence of rheumatoid factor, disease activity score and disease duration. RA Patients (120) and healthy controls (53) were evaluated for the oxidant—antioxidant status by monitoring ROS production, biomarkers of lipid peroxidation, protein oxidation and DNA damage. The level of various enzymatic and non-enzymatic antioxidants was also monitored. Correlation analysis was also performed for analysing the association between ROS and various other parameters.MethodsIntracellular ROS formation, lipid peroxidation (MDA level), protein oxidation (carbonyl level and thiol level) and DNA damage were detected in the blood of RA patients. Antioxidant status was evaluated by FRAP assay, DPPH reduction assay and enzymatic (SOD, catalase, GST, GR) and non-enzymatic (vitamin C and GSH) antioxidants.ResultsRA patients showed a higher ROS production, increased lipid peroxidation, protein oxidation and DNA damage. A significant decline in the ferric reducing ability, DPPH radical quenching ability and the levels of antioxidants has also been observed. Significant correlation has been found between ROS and various other parameters studied.ConclusionRA patients showed a marked increase in ROS formation, lipid peroxidation, protein oxidation, DNA damage and decrease in the activity of antioxidant defence system leading to oxidative stress which may contribute to tissue damage and hence to the chronicity of the disease.     

Features of regulating delta sleep-inducing peptide by free radical processes in tissue and erythrocyte membranes in intact animals and under stress

In activity the comparative analysis of metabolic effects delta--sleep inducing peptide (DSIP) in tissues and erythrocytes of intact rats and under cold stress is conducted. The regulation effect of DSIP in attitude of free radical processes will be realised through modulation the prooxidant--antioxidant balance: both for intact animal, and at stress. Exogenous DSIP increases the antioxidant system activity in tissues of brain, liver and blood in standard conditions and under cold stress. The anti-stress effect of DSIP is directed as on increase of power endogenic enzymatic antioxidant system activity, specially glutathione peroxidase activity, and not enzymatic of antioxidant protection. The DSIP renders different influence on activity of prooxidant enzymes: for intact animal boosts the myeloperoxidase activity in blood neutrophils, not rendering essential influencing on the xanthine oxidase activity in tissues of brain, liver and activates the myeloperoxidase activity, depresses the xanthine oxidase activity for rats at stress. The membranotropic effect of DSIP in the norm and under stress is connected to increase of stability of protein--lipid interplays. The membranostabilizing effect of DSIP in conditions of stress is characterized decrease of polarity of lipid phase and negative surface charge of erythrocyte membranes, modified in course of lipid peroxidation.