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Effect of quercetin and genistein on copper- and iron-induced lipid peroxidation in methyl linolenate.

The single and combined effects of two abundant flavonoids, namely quercetin and genistein, were investigated according to their ability to inhibit the oxidation of methyl linolenate via Fenton's pathway. Antioxidative activity was determined by oxidizing methyl linolenate suspended in a buffer solution with either Fe2+ (50 microM) or Cu2+ (50 microM) and hydrogen peroxide (0.01 mM) without or with a flavonoid sample (10 or 20 microM). Lipid peroxidation products were measured by the thiobarbituric acid (TBA) assay and the amounts of thiobarbituric acid-reactive substances (TBARS) were calculated from a calibration curve using 1,1,3,3-tetraethoxypropane as the standard. Both quercetin and genistein at the 10 or 20 microM level decreased lipid peroxidation significantly compared with their respective controls. Of the two flavonoids tested, quercetin had a more marked effect on inhibiting lipid peroxides. Peroxidation products for the control samples were higher for the Fe2+-treated samples compared with the Cu2+ samples. Combination of both flavonoids at the same dose levels continued to decrease lipid peroxidation, the effect being the same for both metal ions. The data suggest that the combined flavonoids offered better protection than the single treatments and this may be attributed to the better radical scavenging or increased chelating capabilities of the combined over the single treatments. The differences in peroxide levels for the single treatment of quercetin compared with the genistein-treated samples may reflect the structural differences between these compounds in combating oxidative stress.

Antioxidants↗
PubMed2003

Melatonin reduces Fenton reaction-induced lipid peroxidation in porcine thyroid tissue.

Free radicals and reactive oxygen species (ROS) participate in physiological and pathological processes in the thyroid gland. Bivalent iron cation (ferrous, Fe(2+)), which initiates the Fenton reaction (Fe(2+) + H2O2 --> Fe(3+) + *OH + OH(-)) is frequently used to experimentally induce oxidative damage, including that caused by lipid peroxidation. Lipid peroxidation is involved in DNA damage, thus indirectly participating in the early steps of carcinogenesis. In turn, melatonin is a well-known antioxidant and free radical scavenger. The aim of the study was to estimate the effect of melatonin on basal and iron-induced lipid peroxidation in homogenates of the porcine thyroid gland. In order to determine the effect of melatonin on the auto-oxidation of lipids, thyroid homogenates were incubated in the presence of that indoleamine in concentrations of 0.0, 0.00001, 0.0001, 0.001, 0.01, 0.1, 0.25, 0.5, 1.0, 2.5, or 5.0 mM. To study melatonin effects on iron-induced lipid peroxidation, the homogenates were incubated in the presence of FeSO(4) (40 microM) plus H2O2 (0.5 mM), and, additionally, in the presence of melatonin in the same concentrations as above. The degree of lipid peroxidation was expressed as the concentration of malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) per mg protein. Melatonin, in a concentration-dependent manner, decreased lipid peroxidation induced by Fenton reaction, without affecting the basal MDA + 4-HDA levels. In conclusion, melatonin protects against iron + H2O2-induced peroxidation of lipids in the porcine thyroid. Thus, the indoleamine would be expected to prevent pathological processes related to oxidative damage in the thyroid, cancer initiation included.

Animals↗
PubMed1996

Interaction of ferric complexes with NADH-cytochrome b5 reductase and cytochrome b5: lipid peroxidation, H2O2 generation, and ferric reduction.

NADH is reactive in interacting with iron and liver microsomes to catalyze the formation of reactive oxygen species. NADH-dependent microsomal electron transfer involves the enzymes NADH-cytochrome b5 reductase and cytochrome b5. Experiments were carried out to evaluate the ability of reconstituted systems containing purified reductase in the absence or presence of b5 to reduce several ferric complexes, to generate H2O2, and to catalyze lipid peroxidation. The reductase directly reduced ferric-EDTA; addition of b5 inhibited this reduction probably due to competition for the reductase. Cytochrome b5 was required for reduction of low (5 microM) and high (50 microM) concentrations of ferric-histidine and ferric-ammonium sulfate and low concentrations of ferric-ATP. The reductase could interact directly with high (50 microM) concentrations of ferric-ATP. Peroxidation of phospholipids extracted from liver microsomes by the reductase required b5. Molar ratios of b5 to reductase approximating those found in liver microsomes (e.g., 10) were effective in catalyzing lipid peroxidation and ferric reduction. The role of b5 in catalyzing lipid peroxidation appears to involve reduction of the ferric catalyst to help form an initiation complex and degradation of lipid hydroperoxides by the hemeprotein to catalyze propagation of the peroxidation cycle. In contrast to results with microsomes, lipid peroxidation by the complete reconstituted system was sensitive to super-oxide dismutase; this sensitivity was decreased if the reconstituted system was dialyzed overnight to form vesicular preparations, indicating that accessibility of enzymes to sites of peroxidation was important. High rates of H2O2 formation were observed in the presence of ferric-EDTA plus reductase; rates of H2O2 formation with the other ferric complexes were low even in the presence of b5. These results indicate that the ability of NADH reductase and cytochrome b5 to interact with various ferric complexes depends on the nature of the chelating agent used to complex the iron and on the concentration of the iron.

Adenosine Triphosphate↗
PubMed1996

Effect of elevated glucose concentrations on cellular lipid peroxidation and growth of cultured human kidney proximal tubule cells.

This study has examined whether elevated glucose can induce lipid peroxidation and contribute to the inhibition of cell growth in human kidney proximal tubule(HPT) cells. HPT cells were cultured in media containing glucose concentrations of 8 mM (control), 25 mM, and 50 mM. Lipid peroxidation was assessed by the thiobarbituric acid reactivity and cell growth was assessed by 3H-thymidine uptake. Results show decreased (59%, p < 0.01) growth of HPT cells cultured in 50 mM glucose. Cells cultured in 50 mM mannitol did not show any growth inhibition, suggesting that the decreased cell growth associated with glucose is not due to osmolarity changes. There was an increase (108%, p < 0.02) in lipid peroxidation in cells cultured with high levels of glucose (50 mM) compared with controls and cells cultured with 50 mM mannitol. To examine if membrane lipid peroxidation or malondialdehyde (MDA, an end product of lipid peroxidation) has any role in the inhibition of cell growth, we examined the effect of tertiary butylhydroperoxide (TBH, known to cause lipid peroxidation and generate MDA) on the growth of HPT cells. TBH decreased cell growth (49, 17 and 3% of controls at 0.1, 0.25, and 0.5 mumole TBH/ml medium). Similarly, a marked reduction in the growth was observed with exogenous MDA (72, 69 and 34% of controls at 0.1, 0.25, and 0.5 mumole MDA/ml medium). This suggests that elevated glucose can induce membrane lipid peroxidation and accumulation of MDA, which in turn can inhibit cellular growth and contribute to the altered structure and function of HPT cells in diabetes.

Cell Division↗
PubMed1983

Initiation of lipid peroxidation by a peroxidase/hydrogen peroxide/halide system.

A lactoperoxidase/H2O2/halide system caused the initiation of linoleate peroxidation as indicated by diene conjugation. Coupled lipid peroxidation was accelerated by iodide, chloride and bromide ions at pH 4.0 and 6.2. No peroxidation occurred in the presence of H2O2 or lactoperoxidase alone. The rate of linoleate peroxidation by lactoperoxidase in the presence of chloride depended on the concentration of H2O2. Linoleate peroxidation by the enzymatic system was inhibited by high concentration of H2O2 by methionine, tryptophan and BHT. Oxygen was absorbed during peroxidation and the major products were the 13-hydroperoxides. The mechanisms of the initiation of lipid peroxidation by a peroxidase/H2O2/halide system are discussed.

Chemical Phenomena↗
PubMed1982

Copper(II)-catalyzed lipid peroxidation in liposomes and erythrocyte membranes.

Cu++ was uniquely capable of catalyzing the peroxidation of rat erythrocyte membrane lipid in the presence of 10 mM H2O2, whereas several other transition metal ions were without significant effect. In contrast, peroxidation of soybean phospholipid liposomes could be catalyzed with decreasing efficiency by Co++, Cu++, Pb++, or Cr+++ also in the presence of H2O2. The effect of imidazole on Cu++- catalyzed lipid peroxidation was stimulatory in liposomes and inhibitory in membrane preparations, whereas EDTA, histidine, citrate and alanine inhibited peroxidation in both systems. EDTA could stop the peroxidation after initiation, but catalase could not, indicating that Cu++ alone was necessary for the propagation of the chain reaction. Competitive inhibition studies with various scavengers of hydroxyl radicals or singlet oxygen and the absence of significant reaction enhancement by D2O indicated that neither of these reactive oxygen species was a major mediator in the Cu++-H2O2 oxidative system. A copper-oxygen complex may be directly involved in the initiation of peroxidation. Normal erythrocyte membranes and phospholipid liposomes also differ in their sensitivities toward external oxidative stress. In the absence of H2O2, CU++ (0.2 mM) was capable of catalyzing lipid peroxidation in liposomes, aged erythrocyte membranes and membranes from vitamin-E-deficient rats; however, freshly prepared membranes from control rats and liposomes containing alpha-tocopherol required H2O2 greater than 2 mM for the catalytic effect of Cu++ to be observed.

Animals↗
PubMed1991

Lipid composition and peroxide levels of mucosal cells in the rat large intestine in relation to dietary fat.

To examine whether dietary fat alters membrane lipid composition and peroxidation of polyunsaturated fatty acids in "non-proliferative" and "proliferative" cells in the large intestine, Sprague-Dawley rats were fed diets providing a polyunsaturated-to-saturated fatty acid ratio of 1.2 or 0.3 at a high or low level of fat intake for a 25-day period. Cell populations were isolated and the effect of dietary fat on membrane polyunsaturated fatty acid content and peroxide levels was determined. Neither fat level nor fatty acid composition of diet influenced total cholesterol, total phospholipids, and percentage of phospholipid classes in membrane phospholipids. Feeding the high fat and/or high polyunsaturated-to-saturated fatty acid ratio diet increased polyunsaturated fatty acid content of mucosal cell phospholipids. Increase in polyunsaturated fatty acid content was paralleled by a decrease in the monounsaturated fatty acid content of mucosal cell phospholipids. Membrane content of total saturated fatty acids was not significantly affected by diet. Variation in phospholipid fatty acid composition between "non-proliferative" and "proliferative" cells was observed. Lipid peroxide levels in mucosal cell lipid fractions were altered by dietary fat treatment. Animals fed high fat diets, compared to groups fed low fat diets, exhibited higher membrane peroxide levels when results are expressed as nmol/mg protein. Higher peroxide levels were observed in mucosal cells for rats fed high polyunsaturated-to-saturated fatty acid ratio diets when results were expressed per nmol of phospholipid. It is concluded that changes in fat level and fatty acid composition of the diet alters the mucosal cell membrane lipid composition in the rat large intestine and influences susceptibility of mucosal cell lipid to peroxidation. Further research is required to delineate which dietary factors--fat level, polyunsaturated-to-saturated fatty acid ratio, or both--have a primary influence on the degree of lipid peroxidation.

Animals↗
PubMed1989

Studies of ascorbate-dependent, iron-catalyzed lipid peroxidation.

We have previously observed that both Fe(II) and Fe(III) are required for lipid peroxidation to occur, with maximal rates of lipid peroxidation observed when the ratio of Fe(II) to Fe(III) is approximately one (J. R. Bucher et al. (1983) Biochem. Biophys. Res. Commun. 111, 777-784; G. Minotti and S. D. Aust (1987) J. Biol. Chem. 262, 1098-1104). Consistent with the requirement for both Fe(II) and Fe(III), ascorbate, by reducing Fe(III) to Fe(II), stimulated iron-catalyzed lipid peroxidation but when the ascorbate concentration was sufficient to reduce all of the Fe(III) to Fe(II), ascorbate inhibited lipid peroxidation. The rates of lipid peroxidation were unaffected by the addition of catalase, superoxide dismutase, or hydroxyl radical scavengers. Exogenously added H2O2 also either stimulated or inhibited ascorbate-dependent, iron-catalyzed lipid peroxidation apparently by altering the ratio of Fe(II) to Fe(III). Thus, it appears that the prooxidant effect of ascorbate is related to the ability of ascorbate to promote the formation of a proposed Fe(II):Fe(III) complex and not due to oxygen radical production. The antioxidant effect of ascorbate on iron-catalyzed lipid peroxidation may be due to complete reduction of iron.

Animals↗
PubMed1991

Fluorescence characteristics of peroxidation products in porcine intestinal brush-border membranes.

Treatment of the porcine intestinal brush-border membranes with 100 microM ascorbic acid and 10 microM Fe2+ in the presence of various concentrations of tert-butyl hydroperoxide (t-BuOOH) resulted in a marked fluorescence development at 430 nm, depending on the hydroperoxide concentration. This fluorescence formation was closely related to lipid peroxidation of the membranes as assessed by formation of conjugated diene. However there is no linear relation between thiobarbituric acid-reactive substances (TBARS) and fluorescence formation. On the other hand, fluorescence formation in the membranes by treatment with ascorbic acid/Fe2+ or t-BuOOH alone was negligible. The results with antioxidants and radical scavengers suggest that ascorbic acid/Fe2+/t-BuOOH-induced lipid peroxidation of the membranes is mainly due to t-butoxyl and/or t-butyl peroxy radicals. Most TBARS produced during the peroxidation reaction were released from the membranes, but fluorescent products remained in the membrane components. The fluorescence properties of products formed by lipid peroxidation of the membranes were compared with those of products derived from the interaction of malondialdehyde (MDA) or acetaldehyde with the membranes. The fluorescence products in the acetaldehyde-modified membranes also exhibited the emission maximum at 430 nm, while the emission maximum of MDA-modified membranes was 470 nm. The fluorescence intensity of MDA-modified membranes was markedly decreased by treatment with 10 mM NaBH4 but that of the peroxidized or acetaldehyde-modified membranes was enhanced by about two-fold with the treatment. In addition, a pH dependence profile revealed that the fluorescence intensity of the peroxidized or acetaldehyde-modified membranes decreases with increasing pH of the medium, whereas that of MDA-modified ones did not change over the pH range from 5.4 to 8.0. On the basis of these results, the fluorescence properties of products formed in the intestinal brush-border membranes by lipid peroxidation are discussed.

Animals↗
PubMed1991

Inhibition of iodoacetamide and t-butylhydroperoxide toxicity in LLC-PK1 cells by antioxidants: a role for lipid peroxidation in alkylation induced cytotoxicity.

Previously we reported that thiol depletion and lipid peroxidation were associated with the cytotoxicity of nephrotoxic cysteine S-conjugates, a group of toxins which kill LLC-PK1 cells after metabolic activation and covalent binding. To determine if this is a general mechanism of cytotoxicity in these cells, we compared the effect of antioxidants, an iron chelator, and a thiol reducing agent on the toxicity of an alkylating agent, iodoacetamide (IDAM), and an organic peroxidant, t-butylhydroperoxide (TBHP). IDAM or TBHP toxicity was concentration (0.01 to 1.0 mM) and time (1 to 6 h) dependent. Both toxins caused lipid peroxidation which occurred prior to cell death as determined by leakage of lactate dehydrogenase (LDH). The alkylating agent IDAM bound to cellular macromolecules and depleted cellular non-protein thiols almost completely by 1 h, while LDH release occurred first at 2 to 3 h. The toxicity of IDAM and TBHP was inhibited by the antioxidants DPPD, BHA, BHQ, PGA, and BHT and the iron chelator deferoxamine. However, DPPD blocked TBHP- and IDAM-induced lipid peroxidation and toxicity without affecting binding and depletion of cellular nonprotein thiols. Furthermore, the thiol reducing agent dithiothreitol was able to block lipid peroxidation and toxicity. Therefore it is possible that with an alkylating agent, depletion of cellular nonprotein thiols cooperates with covalent binding and contributes to lipid peroxidation and cell death. There appear to be common elements in the toxicity of alkylating agents and organic peroxidants in LLC-PK1 cells.

Alkylating Agents↗
PubMed1989

Influence of cardioprotective cyclooxygenase and lipoxygenase inhibitors on peroxidative injury to myocardial-membrane phospholipid.

Oxygenase-catalyzed and non-enzymatic polyunsaturated fatty acid peroxidations have potential pathogenic roles in ischemic-reperfusion damage to the myocardium. Certain oxygenase inhibitors protect heart muscle from irreversible ischemic injury, and some antiperoxidants can inhibit oxygenase enzymes. We investigated the antiperoxidative abilities of eight anti-ischemic, cardioprotective oxygenase inhibitors to prevent myocardial-membrane phospholipid peroxidation through superoxide-driven, iron-promoted reactions with xanthine oxidase as the source of superoxide. Flurbiprofen, ibuprofen, and REV-5901-5 did not affect peroxidation at concentrations up to 1000 microM. BW755C, AA-861, nafazatrom, dipyridamole, and propyl gallate did protect and cardiac lipids against oxidative injury in a concentration-dependent manner with respective and antiperoxidant IC50 values (concentrations at which peroxidation was inhibited by 50%) of 0.22, 1.25, 3.0, 3.6 and 50 microM. Catechin and phenidone, known oxygenase inhibitors not yet evaluated as anti-ischemic agents, were also found to be antiperoxidants at low micromolar concentrations. Four cyclooxygenase inhibitors ineffective against myocardial infarction (aspirin, indomethacin, naproxen, and sulfinpyrazone) evidenced no antiperoxidant properties at concentrations up to 500 microM. The oxygenase inhibitor-antiperoxidants identified could neither quench superoxide radical nor inhibit xanthine oxidase. However, they were able to interrupt the propagation of an on-going peroxidation reaction. Their antiperoxidant profiles resembled those of known antioxidants, such as alpha-tocopherol, which inhibit peroxidation by intercepting lipid free-radical intermediates. These data raise the possibility that at least some oxygenase inhibitors could exert cardioprotective effects by directly influencing the sensitivity of myocardial-membrane phospholipid to peroxidative injury. Consequently, recognition of the antiperoxidant properties of these agents may aid dissection of their physiological and pharmacological actions.

Aspirin↗
PubMed1991

The inhibition of lipid peroxidation by cinnarizine. Possible implications to its therapeutic and side-effects.

Cinnarizine has antivasoconstrictor properties and improves red-cell deformability. Its major side-effects are the induction of extrapyramidal reactions. It is a calcium antagonist, but it was suggested that its effects may depend on other mechanisms, namely on antiperoxidant properties. We have studied these properties in different biological systems, intact red-cells included. The occurrence of lipid peroxidation was determined by the formation of 2-thiobarbituric acid reactive products. Cinnarizine was found to inhibit spontaneous lipid peroxidation in rat liver homogenates, copper-induced lipid peroxidation in human plasma and copper-induced and hydrogen peroxide-induced lipid peroxidation in human red-cells. In red-cells, the inhibition of lipid peroxidation is accompanied by the inhibition of hemolysis. Copper-induced red-cell lipid peroxidation is 85% inhibited by as little as 5 microM cinnarizine. The antioxidant activity of cinnarizine may contribute to explain some of the effects of this drug.

Animals↗
PubMed1995

Measurement of serum lipid peroxidation during exercise using three different methods: diene conjugation, thiobarbituric acid reactive material and fluorescent chromolipids.

Serum lipid peroxidation was measured by three different methods (diene conjugation, DC; thiobarbituric acid reactive material, TBARM; and fluorescent chromolipids, FC) during physical exercise of different duration. The aim of the study was to investigate which of the three methods is the most representative in measuring oxidative stress after physiological stimulus (physical exercise) in man. In general, diene conjugation is a measure of early events of lipid peroxidation reactions, TBARM measures end products of lipid peroxidation and FC are products formed by reaction of end products of lipid peroxidation with the amino groups. In trial I, 8 subjects ran 1 km with maximal speed; in trial II, 7 subjects ran 10 km with maximal speed; in trial III, 9 subjects ran 27 km with maximal speed, and in trial IV, 5 subjects cycled 8 days in competition, altogether 1061 km biking. In each trial venous blood samples were taken before and immediately after the exercise. In trials II, III, and IV serum DC concentration increased by 14% (P < 0.05), 11% (P < 0.01), and 25% (P < 0.05), respectively, during the exercise. FC or TBARM did not change in the trials. We conclude that DC as a measure of the early phase of lipid peroxidation may be less affected by protective antioxidant functions than FC and TBARM methods, which both measure end products of lipid peroxidation. Therefore, DC may be the most sensitive of the three methods to estimate serum lipid peroxidation induced by exercise in man.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Effect of clofibrate treatment on lipid peroxidation in rat liver homogenate and subcellular fractions.

1. A study was made of the effect of hypolipidemic drug clofibrate on the level of lipid peroxidation in homogenates and subcellular fractions of rat liver. The intensity of lipid peroxidation was measured using chemiluminescence technique and malondialdehyde formation. 2. It was shown that under the action of clofibrate the levels of Fe/ADP-ascorbate-, as well as t-butyl hydroperoxide (Bu'OOH)-induced lipid peroxidation were decreased in the whole and "post-nuclear" liver homogenates. Dilution of the homogenates prevented depressing effect of clofibrate on lipid peroxidation. 3. Clofibrate significantly decreased the level of the Bu'OOH-dependent lipid peroxidation, but did not affect the activity of the Fe/ADP-ascorbate-induced reaction in rat liver mitochondria and microsomes. 4. Peroxidative alteration of membrane lipids in vivo was evaluated by determining the extent of conjugated dienes formation (absorption at 233 nm). It was shown that clofibrate did not increase the level of ultraviolet absorption of lipids from rat liver subcellular fractions. 5. The data obtained indicate that cytosol from the clofibrate treated rat liver contains a factor(s) which prevents lipid peroxidation in the mitochondria and microsomes.

Animals↗
PubMed1995

Differential effects of endothelial cell fatty acid modification on the sensitivity of their membrane phospholipids to peroxidation.

In order to study the relationship between the fatty acid (FA) composition of human umbilical vein endothelial cells (HUVEC) and their susceptibility to oxidative stress, we modified their FA composition by long-term culturing in media supplemented with a saturated, monounsaturated, or polyunsaturated FA. Sensitivity of the cellular phospholipids to peroxidation was monitored by measuring conjugated diene formation and decrease of polyunsaturated FAs induced by CuSO4 and H2O2 in liposomes prepared from the respective phospholipid extracts. The extent of phospholipid peroxidation was found to increase with increasing content of polyunsaturated FAs. In addition, the sensitivity of individual polyunsaturated FAs to peroxidation was directly proportional to the number of double bonds present. However, no unequivocal relationship was observed between conjugated diene formation and the phospholipid unsaturation index (an indicator for the combined effect of number of double bonds and polyunsaturated FA contents of the membrane phospholipids). The results suggest that long-term FA modification of endothelial cells differentially alters the sensitivity of their membrane phospholipids to peroxidation: long-term modification with oleic acid may protect against lipid peroxidation, whereas linoleic acid may increase sensitivity to peroxidation. In contrast to what might be expected, long-term modification of endothelial cells with eicosapentaenoic or docosahexaenoic acid does not increase the sensitivity of phospholipids to peroxidation.

Cells, Cultured↗
PubMed2006

Lipid peroxidation as a source of oxidative damage in Helicobacter pylori: protective roles of peroxiredoxins.

Oxidative stress conditions lead to enzymatic and non-enzymatic unsaturated fatty acid-initiated lipid peroxidation reactions. One exacerbating product is lipid hydroperoxide (LOOH) which itself promotes formation of several additional peroxyl radicals. Helicobacter pylori mutant strains with disruptions in genes encoding the peroxiredoxins, alkyl hydroperoxide reductase (ahpC) and the bacterioferritin comigratory protein (bcp), were more sensitive than the parent strain to oxidizing agents. These mutant strains were particularly sensitive, compared to the wild type, to killing by the unsaturated fatty acid linolenic acid but were not sensitive to the saturated fatty acid palmitic acid. A double mutant strain (ahpC bcp) accumulated more than 3-fold more lipid peroxides than the parent strain, indicating these peroxiredoxins together play a role in detoxifying lipid peroxides. The level of free iron accumulation, a signature of oxidative stress damage, was correlated specifically to organic peroxide-mediated stress by both in vivo and in vitro approaches. Free iron accumulation and concomitant destruction of [Fe-S] cluster-containing proteins (hydrogenase and aconitase) was correlated to damage mediated by exogenous t-butyl peroxide, or separately to intracellular accumulation of lipid peroxides in mutant strains. A major macromolecular target of accumulating lipid peroxides in H. pylori is DNA, as mutant analysis approaches combined with quantitative DNA fragmentation studies and specific DNA damage assessment (i.e. 8-oxoguanine formation) were used to demonstrate that such damage was especially associated with ahpC and ahpC bcp strains.

Bacterial Proteins↗
PubMed2005

Pulmonary surfactant protein A inhibits the lipid peroxidation stimulated by linoleic acid hydroperoxide of rat lung mitochondria and microsomes.

Reactive oxygen species play an important role in several acute lung injuries. The lung tissue contains polyunsaturated fatty acids (PUFAs) that are substrates of lipid peroxidation that may lead to loss of the functional integrity of the cell membranes. In this study, we compare the in vitro protective effect of pulmonary surfactant protein A (SP-A), purified from porcine surfactant, against ascorbate-Fe(2+) lipid peroxidation stimulated by linoleic acid hydroperoxide (LHP) of the mitochondria and microsomes isolated from rat lung; deprived organelles of ascorbate and LHP were utilized as control. The process was measured simultaneously by chemiluminescence as well as by PUFA degradation of the total lipids isolated from these organelles. The addition of LHP to rat lung mitochondria or microsomes produces a marked increase in light emission; the highest value of activation was produced in microsomes (total chemiluminescence: 20.015+/-1.735 x 10(5) cpm). The inhibition of lipid peroxidation (decrease of chemiluminescence) was observed with the addition of increasing amounts (2.5 to 5.0 microg) of SP-A in rat lung mitochondria and 2.5 to 7.5 microg of SP-A in rat lung microsomes. The inhibitory effect reaches the highest values in the mitochondria, thus, 5.0 microg of SP-A produces a 100% inhibition in this membranes whereas 7.5 microg of SP-A produces a 51.25+/-3.48% inhibition in microsomes. The major difference in the fatty acid composition of total lipids isolated from native and peroxidized membranes was found in the arachidonic acid content; this decreased from 9.68+/-1.60% in the native group to 5.72+/-1.64% in peroxidized mitochondria and from 7.39+/-1.14% to 3.21+/-0.77% in microsomes. These changes were less pronounced in SP-A treated membranes; as an example, in the presence of 5.0 microg of SP-A, we observed a total protection of 20:4 n-6 (9.41+/-3.29%) in mitochondria, whereas 7.5 microg of SP-A produced a 65% protection in microsomes (5.95+/-0.73%). Under these experimental conditions, SP-A produces a smaller inhibitory effect in microsomes than in mitochondria. Additional studies of lipid peroxidation of rat lung mitochondria or microsomes using equal amounts of albumin and even higher compared to SPA were carried out. Our results indicate that under our experimental conditions, BSA was unable to inhibit lipid peroxidation stimulated by linoleic acid hydroperoxide of rat lung mitochondria or microsomes, thus indicating that this effect is specific to SP-A.

Animals↗
PubMed2006

Contribution of peroxidized cardiolipin to inactivation of bovine heart cytochrome c oxidase.

The lipid-soluble peroxides, tert-butyl hydroperoxide and peroxidized cardiolipin, each react with bovine cytochrome c oxidase and cause a loss of electron-transport activity. Coinciding with loss of activity is oxidation of Trp19 and Trp48 within subunits VIIc and IV, and partial dissociation of subunits VIa and VIIa. tert-Butyl hydroperoxide initiates these structural and functional changes of cytochrome c oxidase by three mechanisms: (1) radical generation at the binuclear center; (2) direct oxidation of Trp19 and Trp48; and (3) peroxidation of bound cardiolipin. All three mechanisms contribute to inactivation since blocking a single mechanism only partially prevents oxidative damage. The first mechanism is similar to that described for hydrogen peroxide [Biochemistry43:1003-1009; 2004], while the second and third mechanism are unique to organic hydroperoxides. Peroxidized cardiolipin inactivates cytochrome c oxidase in the absence of tert-butyl hydroperoxide and oxidizes the same tryptophans within the nuclear-encoded subunits. Peroxidized cardiolipin also inactivates cardiolipin-free cytochrome c oxidase rather than restoring full activity. Cardiolipin-free cytochrome c oxidase, although it does not contain cardiolipin, is still inactivated by tert-butyl hydroperoxide, indicating that the other oxidation products contribute to the inactivation of cytochrome c oxidase. We conclude that both peroxidized cardiolipin and tert-butyl hydroperoxide react with and triggers a cascade of structural alterations within cytochrome c oxidase. The summation of these events leads to cytochrome c oxidase inactivation.

Animals↗