Effect of nicotinamide on the reactions of peroxide oxidation of biomolecules in the rat brain and erythrocytes in 1,2-dichloroethane toxic injury

It was established that acute poisoning of rats by 1,2-dichloroethane induced considerable changes in lipid peroxidation indices, glutathione content and activity of antioxidant enzymes--superoxidase, catalase, glutathione peroxidase in the brain tissue, erythrocytes and blood plasma. It was shown that nicotinamide in the dose of 200 mg/kg prevented considerable degree of the intoxication caused by 1,2-dichloroethane as well as activation of lipid peroxidation and inhibition of antioxidant defens enzyme activities in tissue of experimental animals.     

The lipid peroxidation system in the retina and brain of rats during early postnatal ontogeny

The content of the lipid peroxidation products in the rat retina and brain tissues during the early postnatal period (20-45 day of life) was estimated. It was shown during this period the content of conjugated dienes was decreased: the content of malondialdehyde and Schiff bases was without changes in the rat retina. At the same time the content of the conjugated dienes and Schiff bases in the brain tissue was proportionally increased. The activity of glutathioneperoxidase and glutathionereductase was decreased in the retina and not changed in brain. In the same period of the life the content of alpha-tocopherol in the retina was increased. We observed also the enhance of the rate of the induced lipid peroxidation in brain and retina of older animals.     

Protective effect of green tea against lipid peroxidation in the rat liver, blood serum and the brain

This paper reports data on the effect of green tea on the lipid peroxidation products formation and parameters of antioxidative system of the liver, blood serum and central nervous tissue of healthy young rats drinking green tea for five weeks. The rats were permitted free access to solubilized extract of green tea. Bioactive ingredients of green tea extract caused in the liver an increase in the activity of glutathione peroxidase and glutathione reductase and in the content of reduced glutathione as well as marked decrease in lipid hydroperoxides (LOOH), 4-hydroksynonenal (4-HNE) and malondialdehyde (MDA). The concentration of vitamin A increased by about 40%. Minor changes in the measured parameters were observed in the blood serum. GSH content increased slightly, whereas the index of the total antioxidant status increased significantly. In contrast, the lipid peroxidation products, particularly MDA was significantly diminished. In the central nervous tissue the activity of superoxide dismutase and glutathione peroxidase decreased while the activity od glutathione reductase and catalase increased after drinking green tea. Moreover the level of LOOH, 4-HNE and MDA significantly decreased. The use of green tea extract appeared to be beneficial to rats in reducing lipid peroxidation products. These results support and substantiate traditional consumption of green tea as protection against lipid peroxidation in the liver, blood serum, and central nervous tissue.     

Changes in the lipid peroxidation activity and intensity of tissue respiration during healing of aseptic and infected wounds in animal experiments

The variance of lipid peroxidation (LPO) was studied by the concentrations of malonic dialdehyde (MDA) in the tissue of wound bed and blood serum on the model of surface musculocutaneous aseptic and infected wounds simulated in 250 rats. The speed of oxygen consumption by isolated wound tissue was determined simultaneously. It was stated that the time course of MDA concentration in wounds and sera as well as tissue respiration in animals with infected wounds differed from those in animals with aseptic wounds. In a whole, MDA levels were found to be higher in cases with infected wounds and of changeable character. The latter animals demonstrated less intensive respiration of granulation tissue. Correlation between the variance of tissue respiration and MDA levels was established as was that of LPO and respiration with the phases of wound process. The findings could be used for the development of pathogenetic therapy and evaluation of its efficacy.     

Age related changes in lipid peroxidation in rat brain and liver

Lipid peroxidation in rat liver, unlike in brain shows wide variations with age. In liver, ascorbic acid content also undergoes wide variations and there is negative correlation between ascorbic acid content and lipid peroxidation. Heat-labile antioxidant factors are present in the cytosol fraction. There is inverse relationship between antioxidant activity and lipid peroxidation in liver.     

Effect of the substances "Ammivit" and "cerloplasmin" on lipid peroxidation products level and of antioxidant system indicators under irradiation

It has been shown, that the total X-ray irradiation in the dozes of 0.5 and 1 Gy influences on the content of lipid peroxidation products and enzymatic activity of antioxidant system in rat spleen and thymus cells. The influence of preparations "AMMIVIT" and "Ceruloplasmin" on these processes is investigated also. So, the animals feeding by the vitamin concentrate "AMMIVIT" have lead to increase of MDA level (a final product of lipid peroxidation) and the overactivity of some antioxidant enzymes in rat spleen and thymus cells. Injection of the preparation "Ceruloplasmin" to experimental animals up 1 hour before the irradiation has normalized LPO intensity and activity of AO enzymes.     

Antioxidative status changes in golden syrian hamsters with experimental metabolic syndrome

Some indices of the antioxidant status (content of the alpha-tocopherol, reduced glutathione and ascorbic acid, activity of the glutathione reductase and aryl-esterase) and lipid peroxidation processes in the liver, blood serum, and some blood serum lipoprotein fractions of the Golden Syrian hamsters of different sex and age status under high-caloric diet were investigated. It has been shown that the hypercaloric diet leads to a decreaseng of reduced glutathione content and increase of the level of lipid peroxidation products in the liver of experimental animals. The ascorbic acids content in male liver is decreased and in female liver is increased. In the blood serum under hypercaloric nutrition the accumulation of lipid peroxidation products and alpha-tocopherol content a decrease in ApoB-lipoproteins and HDL is observed. Simultaneously the ascorbic acid content is increased in the blood serum of all experimental animals. Activation of free-radical oxidation both in the liver, and blood serum is more significant in males compared with females. The data obtained allow to suppose that atherosclerotic complications of metabolic syndrome development may be connected to the lipoprotein oxidant status infringement.     

Lipid peroxidation, antioxidant enzymes, and benzo[a]pyrene-quinones in the blood of rats treated with benzo[a]pyrene

The lipid peroxidation (as malondialdehyde, MDA), activities of superoxide dismutase (SOD) and catalase (CAT), and benzo[a]pyrene (BaP) metabolites were investigated in sera and erythrocytes of male Sprague-Dawley rats treated with BaP (20 mg per rat). MDA levels were significantly increased in sera (16.98+/-3.29 nmol/ml serum, P<0.05) 12 h after BaP treatment and persisted up to 96 h (13.80+/-1. 65 nmol/ml serum, P<0.05), but no significant change in NIDA levels was observed in erythrocytes. SOD and CAT activities were significantly increased in erythrocytes shortly after BaP exposure, and they were slightly decreased in sera, indicating an inverse correlation between lipid peroxidation and antioxidant enzyme activity. BaP and BaP-quinones (BaP-1,6-quinone and BaP-3,6-quinone) were measured in sera during the study period. A rapid increase of unmetabolized BaP was observed in sera (41.27+/-4.14 pmol/ml serum) 3 h after BaP treatment, reaching a peak at 6 h (48.56+/-4.62 pmol/ml serum) followed by a sharp decrease. Formation of the BaP-1, 6-quinone and BaP-3,6-quinone started in sera 3 h after BaP treatment, reached a peak at 24 h (7.23+/-1.02 pmol/ml serum) and 12 h (9.20+/-0.98 pmol/ml serum), respectively, and then decreased gradually. The time-dependent pattern of serum lipid peroxidation and the level of erythrocyte antioxidant enzymes were shown to be related to the concentrations of the BaP-quinone metabolites. These results suggest that BaP treatment, probably via the formation of BaP-quinones, oxidatively altered lipids and antioxidant enzymes in the blood, and might be associated with BaP-related vascular toxicity including carcinogenesis.     

Enzymic lipid peroxidation in the microsomal fraction of rat brain

Abstract: An enzymic lipid peroxidation system has been demonstrated in the microsomal fraction of rat brain and the requirements and optimal conditions for assay determined. The involvement of NADPH-cytochrome c reductase was demonstrated in vesicles reconstituted with lipids extracted from the brain microsomal fraction. Further characterization of the system made use of substances shown to inhibit the liver microsomal system. α-Tocopherol was shown to be an effective inhibitor of lipid peroxidation in the brain microsomal system, whereas Na₂SO₃ had no effect, which is indicative that free radical transfer occurs only in the hydrophobic regions. Neither superoxide dismutase nor catalase inhibited lipid peroxidation. The implications of an NADPH-cytochrome c reductase-dependent lipid peroxidation system that is not linked to a drug hydroxylation system and appears to differ from the liver microsomal system in a number of other ways are discussed.     

Effects of L-arginine and NG-nitro L-arginine methyl ester (L-NAME) on ischemia/reperfusion injury of skeletal muscle, small and large intestines

This study analyzed the effects of L-arginine and non-specific nitric oxide (NO) synthase blocker (L-NAME) on structural and metabolic changes in experimental ischemia/reperfusion injury in the rat. Histopathological evaluation of rat tissues after reperfusion was also performed. The animals were divided into four groups: [1] nonischemic control, [2] ischemia 4 hrs/repefusion 30, 60, 120 min, [3] ischemia/reperfusion after L-arginine administration, [4] ischemia/reperfusion, after L-arginine, and L-NAME. L-arginine (500 mg/kg) and L-NAME (75 micromol/rat/day) were administrated orally for 5 days before experiment. Concentrations of free radicals, CD-62P, CD-54 and malonyl dialdehyde (MDA) in tissues, and MDA and NO levels in sera were determined. Free radical levels significantly increased in reperfused skeletal muscle, small and large intestines. In large bowel, reperfusion increased MDA levels and evoked a rise of endotoxin level while NO levels decreased. Histological studies showed an increase in the number of lymphocytes in both intestines. Administration of L-arginine reduced leukocyte adherence associated with ischemia-repefusion injury, decreased the levels of free radicals and MDA in the examined tissues, and inhibited the release of endotoxins into blood. L-arginine-treated animals showed higher serum NO levels and reduced leukocyte bowel infiltration. Concomitant L-NAME administration reduced serum NO and tissue free radical [corrected] levels, but did not affect intestinal leukocyte infiltration. L-arginine could ameliorate intestinal ischemia/reperfusion injury and constitute a possible protective mechanism by decreasing neutrophil-endothelial interactions, stimulating free radical scavenging and reducing lipid peroxidation.     

Serum antibodies to brain protein antigens in cerebral palsy in children]

Using special brain antigen test-system ELITEST-24, ELISA assays of the serum of children with cerebral palsy were conducted. The data obtained were compared to relevant characteristics of the sera from neurologically and somatically healthy persons and patients with diagnoses of multiple sclerosis, schizophrenia, epilepsy and hepato-cerebral dystrophy according to special PC program VIZUAL and DIAGNOST. High specificity of the cerebral palsy anti-brain antigens reactivity was revealed by ELITEST technique. Moreover, the comparison of the mother-child pair immunoreactivity has been conducted. Evidence for hypothesis of epigenetically performing of children antibodies repertoires by mother-during-pregnancy immune status were obtained. Possible immunopathologic mechanisms of the disease are discussed.     

Oxidative damage increases with age in a canine model of human brain aging

We assayed levels of lipid peroxidation, protein carbonyl formation, glutamine synthetase (GS) activity and both oxidized and reduced glutathione to study the link between oxidative damage, aging and beta-amyloid (Abeta) in the canine brain. The aged canine brain, a model of human brain aging, naturally develops extensive diffuse deposits of human-type Abeta. Abeta was measured in immunostained prefrontal cortex from 19 beagle dogs (4-15 years). Increased malondialdehyde (MDA), which indicates increased lipid peroxidation, was observed in the prefrontal cortex and serum but not in cerebrospinal fluid (CSF). Oxidative damage to proteins (carbonyl formation) also increased in brain. An age-dependent decline in GS activity, an enzyme vulnerable to oxidative damage, and in the level of glutathione (GSH) was observed in the prefrontal cortex. MDA level in serum correlated with MDA accumulation in the prefrontal cortex. Although 11/19 animals exhibited Abeta, the extent of deposition did not correlate with any of the oxidative damage measures, suggesting that each form of neuropathology accumulates in parallel with age. This evidence of widespread oxidative damage and Abeta deposition is further justification for using the canine model for studying human brain aging and neurodegenerative diseases.     

Developmental vitamin D deficiency alters brain protein expression in the adult rat: implications for neuropsychiatric disorders

An increased risk for multiple sclerosis and schizophrenia is observed at increasing latitude and in patients born in winter or spring. To explore a possible link between maternal vitamin D deficiency and these brain disorders, we examined the impact of prenatal hypovitaminosis D on protein expression in the adult rat brain. Vitamin D-deficient female rats were mated with vitamin D normal males. Pregnant females were kept vitamin D-deficient until birth whereupon they were returned to a control diet. At week 10, protein expression in the progeny's prefrontal cortex and hippocampus was compared with control animals using silver staining 2-D gels associated with MS and newly devised data mining software. Developmental vitamin D (DVD) deficiency caused a dysregulation of 36 brain proteins involved in several biological pathways including oxidative phosphorylation, redox balance, cytoskeleton maintenance, calcium homeostasis, chaperoning, PTMs, synaptic plasticity and neurotransmission. A computational analysis of these data revealed that (i) nearly half of the molecules dysregulated in our animal model have also been shown to be misexpressed in either schizophrenia and/or multiple sclerosis and (ii) an impaired synaptic network may be a consequence of mitochondrial dysfunction.     

Age peculiarities in changes of free radical oxidation processes in the brain of rats with hypothyroidism

The objective of the present experiment was to study age peculiarities of free radical protein oxidation and lipid peroxidation in brain of 1.5-month-old and 12-month-old rats with drug-induced hypothyroidism. It has been shown that hypothyroidism in both 1.5-month and 12-month old rat is accompanied by the oxidative stress in the brain. It manifests by an increase of content of lipid peroxidation products and protein carbonyls in mitochondrial and microsomal fractions. Hypothyroidism decreases the prooxidant effect of exercises on the brain mitochondria.     

A model of aluminum exposure associated with lipid peroxidation in rat brain

We have developed a rat model to investigate the relationship between aluminum exposure and aluminum accumulation, and with oxidative damage in brain tissues. Intraperitoneal injections of aluminum lactate for 7 wk (the total aluminum dosage per rat was approx 100 mg) significantly increased aluminum levels in the brain. The concentration of lipid peroxidation products (thiobarbituric acid-reactive substances [TBARS]) also increased in the brain following aluminum lactate injections. No significant correlations between the concentrations of aluminum and of TBARS were found in the whole brain. Subcellular analysis revealed that aluminum lactate injections led to a significant increase in the concentration of aluminum in the mitochondrial fraction but had no significant effect on the concentration of peroxides in any subcellular fraction. These results suggest that aluminum accumulation induced by the aluminum lactate administration associates with the acceleration of lipid peroxidation in rat brain. Furthermore, these data indicate that the pro-oxidant effect of aluminum may be indirect and concentration independent. The experimental conditions used here provide an animal model of aluminum accumulation in the brain that should prove useful for further investigations of the mechanisms of aluminum neurotoxicity.     

Evaluation of in vitro antioxidant activity of Indian bay leaf, Cinnamomum tamala (Buch. -Ham.) T. Nees & Eberm using rat brain synaptosomes as model system

The study investigated the perturbation of oxidant-antioxidant balance in brain synaptosomes of diabetic rats and determined the antioxidant and free radical-scavenging property of the Indian bay leaf. Brain synaptosomes were isolated from control and streptozotocin-induced diabetic animals and oxidative stress parameters were assayed. A methanolic extract of bay leaf (BLE) was tested for the polyphenolic content and antioxidant activity by in vitro assays. A significant increase in the levels of lipids and lipid peroxidation products and a decline in antioxidant potential were observed in diabetic rat brain synaptosomes. The total polyphenolic content of BLE was found to be 6.7 mg gallic acid equivalents (GAE)/100g. BLE displayed scavenging activity against superoxide and hydroxyl radicals in a concentration-dependent manner. Further, BLE showed inhibition of Fe(2+)-ascorbate induced lipid peroxidation in both control and diabetic rat brain synaptosomes. Maximum inhibition of lipid peroxidation, radical scavenging action and reducing power of BLE were observed at a concentration of 220 microg GAE. These effects of BLE in vitro were comparable with that of butylated hydroxyl toluene (BHT), a synthetic antioxidant. It can be concluded that synaptosomes from diabetic rats are susceptible to oxidative damage and the positive effects of bay leaf in vitro, could be attributed to the presence of antioxidant phytochemicals.     

Basal Lipid Peroxidation in Substantia Nigra Is Increased in Parkinson''s Disease

Polyunsaturated fatty acid (PUFA) levels (an index of the amount of substrate available for lipid peroxidation) were measured in several brain regions from patients who died with Parkinson's disease and age-matched control human postmortem brains. PUFA levels were reduced in parkinsonian substantia nigra compared to other brain regions and to control tissue. However, basal malondialdehyde (MDA; an intermediate in the lipid peroxidation process) levels were increased in parkinsonian nigra compared with other parkinsonian brain regions and control tissue. Expressing basal MDA levels in terms of PUFA content, the difference between parkinsonian and control substantia nigra was even more pronounced. Stimulating MDA production by incubating tissue with FeSO4 plus ascorbic acid, FeSO4 plus H2O2, or air alone produced lower MDA levels in the parkinsonian substantia nigra, probably reflecting the lower PUFA content. These results may indicate that an increased level of lipid peroxidation continues to occur in the parkinsonian nigra up to the time of death, perhaps because of continued exposure to excess free radicals derived from some endogenous or exogenous neurotoxic species.     

Developmental vitamin D deficiency alters the expression of genes encoding mitochondrial, cytoskeletal and synaptic proteins in the adult rat brain

Epidemiology has highlighted the links between season of birth, latitude and the prevalence of brain disorders such as multiple sclerosis and schizophrenia. In line with these data, we have hypothesized that ‘imprinting’ with low prenatal vitamin D could contribute to the risk of these two brain disorders. Previously, we have shown that transient developmental hypovitaminosis D induces permanent changes in adult nervous system. The aim of this study was to examine the impact of prenatal hypovitaminosis D on gene expression in the adult rat brain. Vitamin D deficient female rats were mated with undeprived males and the offspring were fed with a control diet after birth. At Week 10, gene expression in the progeny's brain was compared with control animals using Affymetrix gene microarrays. Prenatal hypovitaminosis D causes a dramatic dysregulation of several biological pathways including oxidative phosphorylation, redox balance, cytoskeleton maintenance, calcium homeostasis, chaperoning, post-translational modifications, synaptic plasticity and neurotransmission. A computational analysis of these data suggests that impaired synaptic network may be a consequence of mitochondrial dysfunction. Since disruptions of mitochondrial metabolism have been associated with both multiple sclerosis and schizophrenia, developmental vitamin D deficiency may be a heuristic animal model for the study of these two brain diseases.     

The study of cytokine content and ganglioside metabolism in experimental brain edema

A blood cytokine profile and also the brain content of lipid peroxidation (LPO) products and gangliosides were investigated in rats with experimental brain edema. The development of brain edema was accompanied by the increase in pro-inflammatory and a decrease in anti-inflammatory cytokine content. In parallel, accumulation of LPO products (conjugated dienes, hydroperoxides, and malondialdehyde) was observed. The study of ganglioside content under conditions of experimental brain edema revealed a decrease of their hydrolytic degradation product, sphingosine.