Antioxidant effect of caeruloplasmin on microsomal lipid peroxidation

Microsomal NADPH-dependent lipid peroxidation catalyzed by ADP-Fe³⁺ was inhibited by the addition of caeruloplasmin. The antioxidant effect of caeruloplasmin was independent of the superoxide anion (O^?₂ scavenging activity. Since caeruloplasmin enhanced the function of ADP-Fe³⁺ acting as electron acceptor for microsomal electron transport system, the antioxidant effect of caeruloplasmin is considered to depend on the ferroxidase activity.     

Antiradical and antioxidant effect of arginine and its action on lipid peroxidation in hypoxia

Arginine (0.5 and 1 mu mol) decreased by 14-17% rates of superoxide anion formation in two systems: HADH-phenazine methosulfate and hydroxylamine autooxidation with nitrotetrazolium blue. These concentrations of arginine decreased by 40-50% formation of diene conjugates and Schiff bases in plasma when lipid peroxidation initiated by iron -ascorbate. Arginine administration before hypoxia decreased lipid peroxidation rate in plasma and liver microsomal membranes of rats.     

The antioxidant action of tamoxifen and its metabolites. Inhibition of lipid peroxidation

The anti-oestrogen drug tamoxifen is an inhibitor of lipid peroxidation in rat liver microsomes and in phospholipid liposomes. Its cis isomer and N-desmethyl form are weaker inhibitors, but 4-hydroxytamoxifen is much more powerful. It is possible that the antioxidant property of tamoxifen might contribute to its biological actions.     

Antioxidant protection by haemopexin of haem-stimulated lipid peroxidation.

Haem (ferrous protoporphyrin IX) is a reactive low-molecular-mass form of iron able to participate in oxygen-radical reactions that can lead to the degradation of proteins, lipids, carbohydrates and DNA. Oxygen-radical reactions are likely to occur upon tissue damage. Extracellular fluids rely on antioxidant mechanisms different from those found inside the cell, and circulating proteins limit radical reactions by converting pro-oxidant forms of iron into less-reactive forms. Of the compounds tested, only apohaemopexin and the chain-breaking antioxidant butylated hydroxytoluene inhibited (by more than 90%) haemin-stimulated peroxidation as measured by formation of conjugated dienes, thiobarbituric acid-reactive material from linolenic acid or peroxidation-induced phospholipid fluorescence. Haptoglobin, the haemoglobin-binding serum protein, was ineffective. Conversely, only haptoglobin significantly inhibited haemoglobin-stimulated lipid peroxidation. Iron-salt-induced lipid peroxidation was inhibited only by apotransferrin and the iron-chelator desferrioxamine. All lipid peroxidations were inhibited by the radical scavengers butylated hydroxytoluene and propyl gallate. These findings support the concept that transport and conservation of body iron stores are closely linked to antioxidant protection.     

Antioxidant enzymes and lipid peroxidation in different stages of breast cancer

Oxidative stress resulting from an imbalance between pro-oxidants and anti-oxidants seems to play an important role in human breast carcinogenesis. There are conflicting reports regarding the tissue levels of malondialdehyde (MDA), ascorbic acid and superoxide dismutase (SOD) in breast cancer patients whereas few blood values have been reported. The present study was carried out to observe the changes in serum MDA, serum SOD and plasma ascorbic acid with the stage-wise progression of the disease. Serum MDA and serum SOD levels were found to be increased gradually from Stage I to Stage IV as compared to control group (p < 0.001). The maximum rise was in Stage IV patients. In contrast, mean plasma ascorbic acid levels were low in all stages compared to control group (p < 0.001). The decrease was more pronounced in Stage III and Stage IV. The study would be of immense help for establishing blood based biochemical marker in breast cancer patients.     

Antioxidant action of 2,2,4,6-tetra-substituted 2,3-dihydro-5-hydroxybenzofuran against lipid peroxidation: effects of substituents and side chain

With increasing evidence suggesting the involvement of oxidative stress in various disorders and diseases, the role of antioxidants in vivo has received much attention. 2,3-Dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran (BO-653) was designed, synthesized and has been evaluated as a novel antiatherogenic drug. In order to further understand the action of BO-653 and also radical-scavenging antioxidants in general, the dynamics of inhibition of oxidation by BO-653 were compared with those of the related compounds, 2,3-dihydro-5-hydroxy-2,2-dimethyl-4,6-di-tert-butylbenzofuran (BOB), 2,3-dihydro-5-hydroxy-2,2,4,6-tetramethylbenzofuran (BOM), alpha-tocopherol and 2,2,5,7,8-pentamethyl-6-chromanol (PMC), aiming specifically at elucidating the effects of substituents and side chain length of the phenolic antioxidants. These five antioxidants exerted substantially the same reactivities toward radicals and antioxidant capacities against lipid peroxidation in organic solution. When compared with di-methyl side chains, the di-pentyl side chains of BO-653 reduced its inter-membrane mobility but exerted less significant effect than the phytyl side chain of alpha-tocopherol on the efficacy of radical scavenging within the membranes. Di-tert-butyl groups at both ortho-positions made BO-653 and BOB more lipophilic than di-methyl substituents and reduced markedly the reactivity toward Cu(II) and also the synergistic interaction with ascorbate. The results of the present study together with those of the previous work on the effect of substituents on the stabilities of aryloxyl radicals suggest that tert-butyl group is more favorable than methyl group as the substituent at the ortho-positions and that di-pentyl side chains may be superior to a phytyl side chain.     

Antioxidant effect of vitamin E and glutathione on lipid peroxidation in boar semen plasma

The protective effect of vitamin E and reduced glutathione (GSH) against lipid peroxidation in boar semen plasma was studied. The lipid peroxidation, measured by the test for thiobarbituric acid reactive substances (TBARS), doubled in the presence of the lipid peroxidation Fe²⁺-sodium ascorbate-inducing system. The ascorbate-induced TBARS were inhibited by about 62% through the water-soluble vitamin E analog (TROLOX) and about 57% by GSH. In the in vivo experiments, 7 wk of oraldl-α-tocopherol acetate (1000 IU/d/animal) administration caused a significant fall in the level of the semen plasma TBARS, from 2.2±0.09 to 1.2±0.13 nmol MDA/mL. The semen plasma superoxide dismutase (SOD) and GSSG tended to increase with the time of vitamin E administration, but the increment did not reach a significant level by the seventh week. The vitamin E supplementation significantly increased the number of spermatozoa per 1 cm³ of ejaculate. The protective role of vitamin E and GSH with respect to boar semen against fatty acid peroxidation and a positive influence of vitamin E supplementation on semen quality have been evidenced.     

Antioxidant defenses and lipid peroxidation damage in estivating toads, Scaphiopus couchii

Tissue-specific changes in antioxidant defenses and lipid peroxidation damage were analyzed in spadefoot toads, Scaphiopus couchii, to determine how these responded during estivation, a state of suppressed oxygen consumption. Maximal activities of glutathione-S-transferase, glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase were measured in six organs from 2-month-estivated toads and compared with activities in animals awakened for 10 days after estivation. Activities of many enzymes, particularly the glutathione-linked enzymes, were significantly lower in tissues of estivating toads than in awake toads. This indicates that enzymatic antioxidant defenses are probably modulated in response to the rate of reactive oxygen species generation in tissues, which is proportional to oxygen consumption. Antioxidant enzyme activities were largely insensitive to high urea, which accumulates during estivation, but were inhibited by elevated KCl. Levels of reduced glutathione were also significantly lower in three organs during estivation and all organs, except skeletal muscle, exhibited a higher oxidized/reduced glutathione ratio, indicating a more oxidized state during estivation. Products of lipid peroxidation (conjugated dienes, lipid hydroperoxides) were higher in tissues of estivated than control toads, suggesting accumulated oxidative damage to lipids during dormancy. One enzymatic source of free radical generation, xanthine oxidase, appeared to have little impact because its activity was detectable only in liver and was significantly lower in estivated toads. The data indicate that both enzymatic and metabolite antioxidant defenses in toads are adaptable systems that are modulated in estivating versus awake states. Accepted: 21 October 1997     

Antioxidant effect of diethyldithiocarbamate on microsomal lipid peroxidation assessed by low-level chemiluminescence and alkane production

Different thiol-containing compounds, such as diethyldithiocarbamate (DDC), glutathione, penicillamine, and dithioerythritol have been chosen to study their effect on ascorbate/Fe-ADP-induced lipid peroxidation, detected by low-level chemiluminescence and alkane production. In the concentration range used, these thiols exerted a temporary protection against lipid peroxidation by lengthening the induction period; after overcoming this induction period, no substantial inhibition of either chemiluminescence or alkane production was observed. DDC was effective in protecting against lipid peroxidation in the nanomolar range, whereas the group of other thiol-containing molecules operated in the millimolar range.     

Comparative efficiency of injurious action of radiation and stress on thymus and lipid peroxidation

Exposure to radiation, as well as holding under conditions of limited mobility during 24 h, induced decrease in thymus cell number, increase in number of DNA breaks. The content the products of lipid peroxidation reactive with thiobarbituric acid in blood serum of mice decreased as well. The stress effect is comparable with radiation doses in the range of 50-60 cGy.     

Relationship between the hemolytic action of heavy metals and lipid peroxidation

It is well known that some of the heavy metals have a hemolytic action, but the mechanisms responsible for this effect are not well established. In order to elucidate whether or not the hemolytic action of heavy metal ions is associated with the peroxidation of membrane lipids, the relationship between metal-induced hemolysis and the generation of malonaldehyde has been studied.The results obtained show that metal-induced hemolysis is associated with the development of peroxidative processes in erythrocyte membranes. The peroxidation is caused by metals with and without pro-oxidant catalytic action. The level of the malonaldehyde products rises before the appearance of hemolysis which proves that the development of peroxidative processes precedes but does not result from hemolysis.The suggestion has been made that the peroxidation of membrane lipids is a possible mechanism of damage to the red cell membrane in metal-induced hemolysis.     

Antioxidant activity of the pyridoindole stobadine in liposomal and microsomal lipid peroxidation.

Stobadine, a pyridoindole derivative, is an efficient inhibitor of lipid peroxidation in phosphatidylcholine liposomes and in rat liver microsomes treated with iron/ADP/NADPH as pro-oxidant. Accumulation of thiobarbituric acid-reactive substances (TBARS) or low-level chemiluminescence were taken as a measure of lipid peroxidation and 5 microM stobadine doubled the duration of the lag phase preceding the onset of rapidly increasing chemiluminescence. Inhibition of lipid peroxidation was not observed with tocopherol-deficient microsomes, suggesting that the antioxidant effect of stobadine depends on vitamin E in the membrane. The cis(-) isomer was most effective, with the cis(+) and trans(rac) as well as dehydro- or acetyl derivatives being less active. In liposomes, the presence of reductant (NADPH or ascorbate) protects from the loss of stobadine.     

Protective action of aspirin in experimental myocardial infarction induced by isoproterenol in rats and its effect on lipid peroxidation

The protective action of aspirin in experimental myocardial infraction induced by isoproterenol was studied in rats. Aspirin treated rats showed lower mortality rate and smaller changes in the myocardium on histopathological examination when compared to corresponding animals given isoproterenol alone. Changes were also observed in the different lipid fractions studied. The ratio of cholesterol to phospholipids decreased in the heart in aspirin treated animals when compared to control rats given isoproterenol alone. The levels of lipid peroxide also showed a decrease while the activity of superoxide dismutase (SOD) and catalase registered an increase in the aspirin treated animals given isoproterenol when compared to corresponding animals given isoproterenol alone.     

Antioxidant effect of capsaicin on lipid peroxidation in homogeneous solution,micelle dispersions and liposomal membranes

Abstract

The antioxidant activity of capsaicin (CAP) was measured in the oxidation of methyl linoleate (ML) in homogeneous solution, of ML micelles in aqueous dispersions and also of soybean phosphatidylcholine liposomal membrane, and was compared to that of -tocopherol (-TOH) which is one of the most important antioxidants in vivo. The reactivity of CAP toward galvinoxyl (a model phenoxyl radical) in acetonitrile solution was found to be much smaller than that of -TOH, suggesting that the radical scavenging activity of CAP is much weaker than that of -TOH. In fact, in homogeneous acetonitrile solution where the antioxidant activity is determined primarily by the chemical activity of the antioxidant toward peroxyl radicals, CAP inhibited the oxidation of ML much less efficiently than -TOH and a clear induction period was not observed. The antioxidant activity of CAP was found to be about 60 times smaller than that of -TOH in homogeneous solution. However, in micelle oxidation, the difference in antioxidant activity of the two antioxidants was much smaller than in homogeneous solution. Furthermore, in the membrane, CAP inhibited the oxidation almost as effectively as -TOH. These results suggest that CAP can act as an antioxidant in the biomembrane.     

Antioxidant effect of bovine serum albumin on membrane lipid peroxidation induced by iron chelate and superoxide

Albumin is supposed to be the major antioxidant circulating in blood. This study examined the prevention of membrane lipid peroxidation by bovine serum albumin (BSA). Lipid peroxidation was induced by the exposing of enzymatically generated superoxide radicals to egg yolk phosphatidylcholine liposomes incorporating lipids with different charges in the presence of chelated iron catalysts. We used three kinds of Fe3+-chelates, which initiated reactions that were dependent on membrane charge: Fe3+-EDTA and Fe3+-EGTA catalyzed peroxidation in positively and negatively charged liposomes, respectively, and Fe3+-NTA, a renal carcinogen, catalyzed the reaction in liposomes of either charge. Fe3+-chelates initiated more lipid peroxidation in liposomes with increased zeta potentials, followed by an increase of their availability for the initiation of the reaction at the membrane surface. BSA inhibits lipid peroxidation by preventing the interaction of iron chelate with membranes, followed by a decrease of its availability in a charge-dependent manner depending on the iron-chelate concentration: one is accompanied and the other is unaccompanied by a change in the membrane charge. The inhibitory effect of BSA in the former at high concentrations of iron chelate would be attributed to its electrostatic binding with oppositely charged membranes. The inhibitory effect in the latter at low concentrations of iron chelate would be caused by BSA binding with iron chelates and keeping them away from membrane surface where lipid peroxidation is initiated. Although these results warrant further in vivo investigation, it was concluded that BSA inhibits membrane lipid peroxidation by decreasing the availability of iron for the initiation of membrane lipid peroxidation, in addition to trapping active oxygens and free radicals.     

Asbestos-catalysed lipid peroxidation and its inhibition by desferroxamine.

In an effort to understand the properties of asbestos fibres that might contribute to their being toxic, we incubated three different varieties of asbestos with phospholipid emulsions and looked for evidence of lipid peroxidation. Although all three types of asbestos were able to catalyse lipid peroxidation in the native state, this catalytic activity was inhibited by pre-washing of the asbestos with the iron chelator desferroxamine. This suggests that: lipid peroxidation may be one of the mechanisms by which asbestos produces tissue injury, and treatment with iron chelators might diminish the potential to produce this injury.     

The histamine-liberating action of polymyxin B and its analogs

Histamine-releasing effect of polymyxin B1 and its deacylated analogues has been studied on purified rat mast cells. The structure-activity analysis showed that cyclic peptide fragment and acyl residue of molecule of polymyxin plays an important role in histamine-releasing activity. Histamine release, induced by polymyxin B1 and its analogue was blocked by metabolic inhibitor antimycin A. Preincubation of polymyxin B1 with lipopolysaccharide inhibits in dose-dependent manner polymyxin-induced histamine secretion from rat mast cells.