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At least 1,153 records · Page 64Linked to original sources
PubMed1998

A marked stimulation of Fe2+-initiated lipid peroxidation in phospholipid liposomes by a lipophilic aluminum complex, aluminum acetylacetonate.

In the present study, the efficacy of a lipophilic Al complex, aluminum acetylacetonate, as a stimulator of Fe2+-initiated lipid peroxidation in phospholipid liposomes was examined, and results were compared with those from the liposomes treated with AlCl3. The extent of lipid peroxidation was assessed by the formation of thiobarbituric acid-reactive substances (TBARS). The results indicated that the stimulatory effect of Al complex on Fe2+-initiated lipid peroxidation in phosphatidylcholine liposomes was more effective than that of AlCl3 under the same conditions. The concentration dependence of Al complex on TBARS production showed that the concentration of the complex required to induce half-maximal stimulation of TBARS production was 43 microM. In contrast, the stimulatory effect of AlCl3 was not observed until the AlCl3 concentration is increased above 300 microM. In addition, it was found that there is a linear relationship between the TBARS values and the residual amounts of Fe2+ at an earlier stage (within 2 min after the addition of Fe2+) of the lipid peroxidation in PC liposomes with different concentrations of Al complex, suggesting that Fe2+ oxidation process is closely related to the stimulatory effect of Al complex. The stimulatory effect of Al complex upon the lipid peroxidation completely disappeared by treatment of Al complex-treated liposomes with Triton X-100. The results of fluorescence anisotropy measurements using 12-(9-anthroyloxy)stearic acid-labeled liposomes suggested that treatment of the liposomes with Al complex caused a decrease in their lipid fluidity. Furthermore, it was found that there is a correlation between the extents of the fluorescence anisotropy and the Fe2+ oxidation parameters in the liposomes with different concentrations of Al complex. From these results, it is suggested that the Al effect on Fe2+-initiated lipid peroxidation in the phospholipid liposomes is markedly enhanced by incorporation of Al complex into the liposomal membranes and that an acceleration of Fe2+ oxidation due to a strengthened packing between the acyl chains in the lipid layer may be one possible mechanism for the occurrence of a marked stimulatory effect of Al complex on Fe2+ initiated lipid peroxidation.

Aluminum↗
PubMed1992

Organic peroxides inhibit neutrophil leukotriene B4 biosynthesis.

Leukotriene B4, an autacoid metabolite of arachidonic acid produced by polymorphonuclear neutrophils, induces chemokinesis, chemotaxis, and adhesion of these cells at sites of inflammation. Because neutrophil infiltration is a self-limited process, we hypothesized that oxidized lipid products of neutrophil-damaged tissue might inhibit leukotriene B4 biosynthesis, thereby preventing additional neutrophil infiltration and limiting peroxidative tissue damage. Erythrocyte ghosts exposed to a hydrogen peroxide-generating system served as a model of peroxidized tissue in inflammation and inhibited neutrophil leukotriene B4 production by 50% compared with unoxidized ghosts. Organic peroxides, including tert-butylhydroperoxide, peracetic acid, and linoleic hydroperoxide, resembling the product(s) of tissue membrane peroxidation in lipid solubility and catalase resistance, inhibited leukotriene B4 biosynthesis in a dose-dependent manner (50% inhibitory concentration of 3.9 microM compared to 530 microM for H2O2). Biosynthetic steps prior to the 5-lipoxygenase did not appear to be the site of inhibition. Likewise, the step after the 5-lipoxygenase, the leukotriene A4 hydrolase, was not primarily involved. Thus a possible mechanism for controlling the influx of neutrophils and their oxidative damage during inflammation may be inhibition of the 5-lipoxygenase by catalase-resistant lipid peroxides released by tissue membranes.

Acyltransferases↗
PubMed1995

Vitamin C prevents metal ion-dependent initiation and propagation of lipid peroxidation in human low-density lipoprotein.

Lipid peroxidation and oxidative modification of low-density lipoprotein (LDL) have been implicated as causal factors in the pathogenesis of atherosclerosis, and prevention of LDL oxidation by antioxidants may be an effective strategy to inhibit the progression of the disease. We investigated the effects of the reduced form of vitamin C (L-ascorbic acid, AA) and its two-electron oxidation product (dehydro-L-ascorbic acid, DHA) upon metal ion-dependent oxidative modification of human LDL. We found that low micromolar concentrations of both AA and DHA protect LDL against oxidation induced by Cu2+ or by hemin and hydrogen peroxide. In a dose-dependent manner, AA and DHA prevented the initiation of lipid peroxidation in LDL, as determined by a sensitive and selective assay for lipid hydroperoxides utilizing HPLC with chemiluminescence detection. AA and DHA also preserved the LDL-associated antioxidants alpha-tocopherol, beta-carotene, and lycopene, but not ubiquinol-10. Furthermore, AA was able to stop propagation of lipid peroxidation in LDL, whereas DHA lacked this ability. The addition of 60 microM AA to LDL containing up to 38 nmol/mg protein of pre-formed lipid hydroperoxides led to their rapid disappearance; this activity of AA was dependent on the presence of redox-active copper, but did not lead to the formation of lipid hydroxides, the reduced form of lipid hydroperoxides. Our data show that in Cu(2+)-exposed LDL (i) vitamin C primarily spares, rather than regenerates, alpha-tocopherol and other endogenous antioxidants, except for AA and DHA prevent initiation of lipid peroxidation in LDL; and (iii) AA can terminate lipid peroxidation, thereby protecting partially oxidized LDL against further oxidative modification.

Adult↗
PubMed1992

Protective effects of a 21-aminosteroid against copper-induced erythrocyte and plasma lipid peroxidation.

The 21-aminosteroids, or lazaroids, are a novel class of antioxidant drugs designed to inhibit iron-dependent lipid peroxidation in biological lipid environments. They have been shown to be of therapeutic value in several animal models of traumatic, ischemic and hemorrhagic injury of the central nervous system. Our purpose was to evaluate the ability of 21-aminosteroids to protect human erythrocytes and plasma against oxidative damage in vitro. We found that the 21-aminosteroid U74500A inhibited erythrocyte and plasma lipid peroxidation. U74500A at 1 microM significantly reduced copper-induced and hydrogen peroxide-induced erythrocyte lipid peroxidation by 76.5 and 27.6%, respectively. The inhibition of erythrocyte lipid peroxidation was accompanied by an inhibition of hemolysis. Copper-induced plasma lipid peroxidation was also significantly reduced by as little as 1 microM U74500A. These results suggest that 21-aminosteroids may prove useful in preventive or therapeutic interventions in situations where erythrocyte or plasma components are subjected to oxidative stress and in situations related to copper-induced oxidative damage.

Antioxidants↗
PubMed2005

Mitochondria superoxide dismutase mimetic inhibits peroxide-induced oxidative damage and apoptosis: role of mitochondrial superoxide.

The purpose of this study was to test the hypothesis whether Mito-carboxy proxyl (Mito-CP), a mitochondria-targeted nitroxide, inhibits peroxide-induced oxidative stress and apoptosis in bovine aortic endothelial cells (BAEC). Glucose/glucose oxidase (Glu/GO)-induced oxidative stress was monitored by dichlorodihydrofluorescein oxidation catalyzed by intracellular H(2)O(2) and transferrin receptor-mediated iron transported into cells. Pretreatment of BAECs with Mito-CP significantly diminished H(2)O(2)- and lipid peroxide-induced intracellular formation of dichlorofluorescene and protein oxidation. Electron paramagnetic resonance (EPR) studies confirmed the selective accumulation of Mito-CP into the mitochondria. Mito-CP inhibited the cytochrome c release and caspase-3 activation in cells treated with peroxides. Mito-CP inhibited both H(2)O(2)- and lipid peroxide-induced inactivation of complex I and aconitase, overexpression of transferrin receptor (TfR), and mitochondrial uptake of (55)Fe, while restoring the mitochondrial membrane potential and proteasomal activity. In contrast, the "untargeted" carboxy proxyl (CP) nitroxide probe did not protect the cells from peroxide-induced oxidative stress and apoptosis. However, both CP and Mito-CP inhibited superoxide-induced cytochrome c reduction to the same extent in a xanthine/xanthine oxidase system. We conclude that selective uptake of Mito-CP into the mitochondria is responsible for inhibiting peroxide-mediated Tf-Fe uptake and apoptosis and restoration of the proteasomal function.

Aconitate Hydratase↗
PubMed1992

Penetration of the pulp chamber by carbamide peroxide bleaching agents.

Hydrogen peroxide readily penetrates the pulp chamber of freshly extracted teeth. This study was undertaken to determine whether carbamide peroxide also penetrates the pulp chamber. Freshly extracted teeth were sectioned 2 to 3 mm apical to the cementoenamel junction and the coronal pulpal tissue was removed. Acetate buffer was placed in the pulp chamber to absorb and stabilize any peroxide that might penetrate. The coronal portion of each tooth was immersed in either carbamide peroxide gel or gelled hydrogen peroxide at various concentrations for 15 min at 37 degrees C. The buffer was removed, leukocrystal violet was added, and the optical density of the resulting blue solution was determined spectrophotometrically. Amounts of peroxide found in the pulp chamber after 15 min ranged from 3.3 +/- 0.38 micrograms for the 10% sample to 40.4 +/- 3.51 micrograms for the 30% sample.

Carbamide Peroxide↗
PubMed2000

Roles of oxygen radical production and lipid peroxidation in the cytotoxicity of cephaloridine on cultured renal epithelial cells (LLC-PK1).

To clarify the mechanism of cephalosporin nephrotoxicity, the cytotoxic effects of cephaloridine (CER), a nephrotoxic cephalosporin antibiotic, on the pig kidney proximal tubular epithelial cell line (LLC-PK1) were studied in culture. CER increased the content of hydrogen peroxide and decreased the activity of catalase in the treated cells, followed by an increase in the content of lipid peroxide and decreases in both glutathione peroxidase activity and in the non-protein sulfhydryl content. The levels of NADPH-dependent hydrogen peroxide and superoxide anion production by microsomes prepared from LLC-PK1 cells, and by NADPH-cytochrome P-450 reductase purified from the rat renal cortex were significantly increased by paraquat. The production of these molecules was antagonized by p-chloromer-curibenzoate, an inhibitor of NADPH-cytochrome P-450 reductase. On the other hand, CER did not significantly affect the production of hydrogen peroxide or superoxide anions. These results suggested that the cytotoxic effect of CER on cultured LLC-PK1 cells was due to the increases in hydrogen peroxide and lipid peroxide levels and not microsomal oxygen radical production, and that the mechanism of this cytotoxicity is very different from that of paraquat which induces microsomal oxygen radical production.

Animals↗
PubMed2002

Peroxide interactions with hard tissues: effects on surface hardness and surface/subsurface ultrastructural properties.

Laboratory studies were performed to assess the impact of peroxide bleaching on enamel surface and subsurface physical and ultrastructural properties. Human enamel blocks were prepared, polished, and measured for native color. Cyclic bleaching treatments were carried out with soaks in whole stimulated saliva interspersed with bleaching treatments using bulk bleaching gels from commercial bleaching systems including Opalescence (20% and 10% carbamide peroxide systems) and Crest Whitestrips, a hydrogen peroxide gel formula, at doses of 5.3% and 6.5% hydrogen peroxide. Treatments ranged from conditions of normal use (14 hours as recommended for Crest Whitestrips) to excessive bleaching (70 hours). Controls included nontreated as well as treatments with placebo (not containing peroxide) gels. Surface hardness and confocal laser scanning microscopy (CLSM) techniques were used to characterize the effects of bleaching on the physical properties and ultrastructure of the teeth. Tooth color measurements revealed dose-response bleaching in vitro with the increases in L* and decreases in b* normally expected with effective bleaching. Placebo control treatments did not bleach. Surface hardness measurements showed no decreases associated with tooth bleaching. CLSM measurements also showed no effects from tooth bleaches on the surface or subsurface prism architecture of enamel. This was opposed to significant changes seen with even moderate levels of demineralization associated with the caries process. These studies support: (1) the safety of Crest Whitestrips formulas for enamel surfaces and tooth subsurfaces; and (2) the generic safety of peroxide bleaching of hard tissues associated with conditions of both recommended use and overuse.

Acrylic Resins↗
PubMed2004

Effects of hydrogen peroxide bleaching strip gels on dental restorative materials in vitro: surface microhardness and surface morphology.

OBJECTIVE: This study examined the effects of peroxide tooth bleaching, including Crest Whitestrips hydrogen peroxide gel treatments, on the surface hardness and morphology of common dental restorative treatments. METHODOLOGY: American Dental Association (ADA) recommended dental restorative materials, including amalgam, dental gold, porcelain, glass ionomer, and composites, were prepared according to manufacturers' instructions. A cycling treatment methodology was employed which alternated ex vivo human salivary exposures with bleaching treatments under conditions of controlled temperature and durations of treatment. Bleaching treatments included commercial Crest Whitestrips bleaching gels, which utilize hydrogen peroxide as the in situ bleaching source, and several commercial carbamide peroxide bleaching gels. Control treatments included placebo gels and an untreated group. Crest Whitestrips bleaching included treatment exposures simulating recommended clinical exposures (14 hours), along with excess bleaching simulating exposure to five times suggested Crest Whitestrips use. At the conclusion of treatments, surface microhardness measures and surface morphological assessments with standard and variable pressure (VP-) SEMs were conducted to assess the effects of bleaching exposure on the surface morphology and structural integrity of the restoratives. RESULTS: Surface microhardness and SEM measures revealed no significant deleterious effects on the restoration surfaces from Whitestrips gels. CONCLUSION: These results confirm that tooth bleaching from the selected commercial hydrogen peroxide or carbamide peroxide bleaching systems does not produce changes in surface morphology or microhardness of common dental restorative materials. These results support the clinical safety of the selected commercial bleaching systems to the oral environment, matching results obtained from long-term use of these ingredients applied in dental offices and available in commercial formulations.

Carbamide Peroxide↗
PubMed1998

Fluorophotometric detection of intravitreal peroxides after panretinal laser photocoagulation.

PURPOSE: To develop a highly sensitive method for in vivo quantitation of intravitreal peroxides by vitreous fluorophotometry with 2',7'-dichlorofluorescin (DCFH), a hydrogen peroxide (H2O2)-sensitive fluorescent dye, and to measure peroxides in the vitreous humor after panretinal laser photocoagulation (PRP). METHODS: In the presence of H2O2 and lipid hydroperoxides, nonfluorescent DCFH was oxidized to highly fluorescent 2',7'-dichlorofluorescein (DCF; excitation, 495 nm; emission, 520 nm), which is detectable by vitreous fluorophotometry. Reactions of DCFH, including hematin with various concentrations of H2O2, were investigated in vivo. Fluorophotometry with DCFH was performed 1, 7, 14, and 28 days and 2 months after argon laser PRP. Untreated eyes served as the controls. RESULTS: Exogenously applied H2O2 oxidized DCFH to DCF in a dose-dependent manner, ranging from 6 x 10(-8) mol/l to 6 x 10(-5) mol/l in concentration in vivo. Intravitreal DCF concentration was 83.7 +/- 6.8 nmol/l in control eyes. A significant increase of DCF was detected 1 day after PRP (330.7 +/- 123.8 nmol/l, P < 0.002). The increase peaked on day 7 (352.4 +/- 239.5 nmol/l, P < 0.002) and remained elevated at 2 months after PRP (161.8 +/- 51.4 nmol/l, P < 0.01). CONCLUSIONS: This method allowed a highly sensitive quantitation of intravitreal peroxides in vivo. The authors' findings indicated that PRP induces increased production of peroxides in rabbit vitreous for 2 months. The data suggested that persistently high levels of peroxides in the vitreous humor affect the development of vitreous liquefaction after PRP.

Animals↗
PubMed1988

Effects of radioligand oxidation and ascorbate-induced lipid peroxidation on serotonin-1 receptor assay: use of ascorbate and ethylenediamine tetraacetic acid buffers to prevent (3H)-5-HT binding artifacts.

The effects of ascorbic acid and ascorbate-induced lipid peroxidation upon (3H)-5-HT binding were examined in total membrane fractions prepared from mouse cortex and hippocampus. Low concentrations of ascorbic acid promoted lipid peroxidation of membranes as assessed by malondialdehyde production relative to intermediate concentrations of ascorbate. The actual concentration of ascorbate required for expression of pro-oxidative and antioxidative properties was dependent upon assay conditions such as temperature and ionic constituents. Ascorbate-induced lipid peroxidation was completely prevented by addition of 1 mM ethylenediamine tetraacetic acid (EDTA) and enhanced by GTP at concentrations typically used in binding assays. Marked lipid peroxidation was associated with loss of (3H)-5-HT binding sites with little effect upon affinity of the receptor for the ligand. In contrast, mild lipid peroxidation occurring during the binding assay with the ligand present was associated with a decreased affinity for (3H)-5-HT and the appearance of a curvilinear Scatchard plot. Under assay conditions that prevented ascorbate-induced lipid peroxidation, Scatchard analysis indicated only a single high-affinity binding site for (3H)-5-HT even when assayed with an expanded range of ligand concentrations. Preparation of ligand and assay of (3H)-5-HT binding in the absence of ascorbate resulted in shallow, markedly curvilinear Scatchard plots. These data support the continued use of ascorbate in (3H)-5-HT binding assays to prevent ligand degradation and the addition of 1 mM EDTA to prevent lipid peroxidation from occurring during the binding assay.

Animals↗
PubMed1999

Human erythrocytes are protected against chromate-induced peroxidation.

In previous studies performed in this laboratory it was realized that in a broad concentration range (0.5-8 mM) dichromate does not induced red blood cell (RBC) peroxidation. To investigate the reasons behind RBC protection against chromate-induced peroxidation, the effects of 8 mM dichromate on white ghost and RBC peroxidation, RBC antioxidant system and hemoglobin status, as well as RBC osmotic fragility and morphology, were studied in more detail. It was observed that the peroxidation level induced by dichromate on RBCs is practically negligible when compared with the peroxidation induced in white ghosts. Furthermore, the osmotic fragility of RBCs exposed to dichromate is not altered, but the cells undergo echinocytic transformation, probably due to chromate-induced structural RBC membrane modifications. The activities of catalase, gluthatione peroxidase, and superoxide dismutase of RBCs exposed to dichromate were similar to those observed in controls, but the gluthatione reductase and GSH levels were significantly reduced (P<0. 05). Concomitantly, GSSG and methemoglobin levels increased and NADH-methemoglobin reductase activity decreased. These results indicate that chromate does not induce RBC peroxidation, but does promote echinocytic shape transformation, oxidation of hemoglobin and GSH, and inhibition of gluthatione reductase and methemoglobin reductase. The enzymatic antioxidant defense system and hemoglobin oxidation are probably involved in the mechanism of RBC proctection against chromate-induced peroxidation, as is discussed.

Catalase↗
PubMed1996

Lipid Peroxidation and Membrane Disruption by Vinclozolin in Dicarboximide-Susceptible and -Resistant Isolates of Botrytis cinerea

A dicarboximide-susceptible (DS) isolate and a dicarboximide-resistant (DR) isolate of Botrytis cinerea were compared with regard to spore germination, mycelial growth, cellular leakage, and lipid peroxidation upon treatment with the dicarboximide fungicide vinclozolin. The fungicide inhibited spore germination and mycelial growth of the DS isolate, but not those of the DR isolate. The inhibitory effect of the fungicide was greater on mycelial growth than on spore germination of the DS isolate. Significant cellular leakage from the fungicide-treated DS or DR isolate began to increase after 24 hr incubation, depending on the concentration of the fungicide and the duration of incubation time. However, the magnitude of cellular leakage was much greater from the DS isolate than from the DR isolate. Vinclozolin caused considerable lipid peroxidation in the DS isolate, whereas little or no lipid peroxidation occurred in the DR isolate treated with the fungicide. Lipid peroxidation preceded cellular leakage from the DS isolate following fungicide treatment. The effects of the fungicide on mycelial growth, cellular leakage, and lipid peroxidation of the DS isolate were all reversed by the addition of alpha-tocopherol to the incubation medium. These results demonstrate that vinclozolin causes significant lipid peroxidation and subsequent cellular leakage from a DS isolate, but not from a DR isolate. Furthermore, they suggest that the mechanism of action of dicarboximide fungicides is associated with membrane lipid peroxidation.

Journal Article↗
PubMed1995

Increased susceptibility to degradation by trypsin and subtilisin of in vitro peroxidized myelin proteins.

We examined the possibility that the peroxidative damage to central nervous system myelin produced by reactive oxygen species (ROS), could modify the susceptibility of its proteins to the proteolytic action of proteases such as trypsin and subtilisin. Purified myelin membranes obtained from adult rat brains were "in vitro" peroxidized by two non-enzymatic systems: Fe3+ plus ascorbic acid and Cu2+ plus hydrogen peroxide. Myelin proteins were severely affected by peroxidation. There was an increase in the amount of carbonyl groups (CO), accompanied by an enhanced susceptibility to degradation by trypsin and subtilisin of myelin basic proteins (MBP) and of the major proteolipid protein (PLP). The effect upon the degradation of myelin protein is a possible consequence of the appearance in the structure of myelin proteins of peroxidative modifications that contribute to the recognition by proteolytic enzymes. This hypothesis is supported by the fact that if peroxidation of myelin membranes is done in the presence of EDTA, both CO formation and increased sensitivity to enzymatic breakdown disappear. These results suggest that the appearance of abnormal post-translational modifications in the myelin membrane produced by peroxidation could constitute a putative mechanism of modulating the capacity of myelin proteins to be metabolized by proteases.

Animals↗
PubMed2000

The developmental transition to flowering represses ascorbate peroxidase activity and induces enzymatic lipid peroxidation in leaf tissue in Arabidopsis thaliana.

Leaf senescence in many plant species is associated with increased oxidative damage to cellular macromolecules by reactive oxygen species (ROS). Since ROS levels and their damage products in many plants are known to increase during senescence, it is possible that these changes are due to a decline in the levels of certain antioxidant enzymes. Using specific assays, we find that the developmental transition to bolting and flowering is associated with up to a 5-fold decline in ascorbate peroxidase activity and an increase in chloroplastid superoxide dismutase. As expected, these changes are associated with a measured increase in lipid peroxidation products. By HPLC separation of the products, we identified the different positional isomers and find that stereospecific lipid peroxidation occurs after the bolting transition. The product distribution suggests that enzyme-mediated lipid peroxidation, via a lipoxygenase, is responsible for the observed increase. Surprisingly, though consistent with the known induction of antioxidant defenses by hydrogen peroxide, the activity of APX rebounds with further development (reproduction and seed setting) and this increase (up to 5-fold) is associated with declines in lipid peroxidation and with the onset of visible senescence symptoms. Thus, in Arabidopsis, ROS increases are associated with the developmental transition to flowering, perhaps due to programmed declines in APX activity, and apparently lead to the oxidative activation of lipoxygenase and subsequent lipid peroxidation. The reactivation of APX at later stages appears to help reduce the lipid peroxidation rate, although the senescence program continues unabated.

Journal Article↗
PubMed2003

Peroxide electroreduction on bi-modified Au surfaces: vibrational spectroscopy and density functional calculations.

The mechanism of the electroreduction of peroxide on Bi-submonolayer-modified Au(111) surfaces is examined using surface-enhanced Raman scattering (SERS) measurements along with detailed density functional theory (DFT) calculations. The spectroscopy shows the presence of Bi-OH and Bi-O species at potentials just positive of that where peroxide is reduced. These species are not present in solutions absent either peroxide or Bi. DFT calculations show that peroxide is unstable relative to Bi-OH when Bi is present in the (2 x 2) configuration on Au(111) known from previous work to be catalytically active. The spacing between Bi adatoms is such that peroxide association with two Bi cannot occur without O-O bond cleavage. The full Bi monolayer is catalytically inactive and exhibits none of the Bi-OH or Bi-O signals seen for the active surface. The calculations show that as the Bi coverage becomes greater and the Bi adatom spacing becomes smaller, peroxide can adsorb on Bi without O-O bond rupture. These results indicate an important role for M-OH species in peroxide electroreduction.

Journal Article↗
PubMed1979

Effects of diffusible products of peroxidation of rat liver microsomal lipids.

The effects on cellular structures of products of peroxidation of rat liver microsomal lipids were investigated. A system containing actively peroxidizing liver microsomal fraction was separated from a revealing or target system by a dialysis membrane. The target system, contained in the dialysis tube, consisted of either intact cells (erythrocytes) or subcellular fractions (liver microsomal fraction). When liver microsomal fractions were incubated with NADPH (or an NADPH-generating system), lipid peroxidation, as measured by the amount of malonaldehyde formed, occurred very rapidly. The malon-aldehyde concentration tended to equilibrate across the dialysis membrane. When the target system consisted of erythrocytes, haemolysis occurred abruptly after a lag phase. The lysis was greatly accelerated when erythrocytes from vitamin E-deficient rats were used, but no haemolysis was observed when erythrocytes from vitamin E-treated rats were used. When, in the same system, freshly prepared liver microsomal fractions were exposed to diffusible factors produced by lipid peroxidation, the glucose 6-phosphatase activity markedly decreased. A similar decrease in glucose 6-phosphatase activity, as well as a smaller but significant decrease in cytochrome P-450, was observed when the target microsomal fractions were exposed to diffusible factors derived from the peroxidation of liver microsomal lipids in a separate preincubation step. These and additional experiments indicated that the toxicological activity is relatively stable. Experiments in which the hepatic microsomal fractions destined for lipid peroxidation contained radioactively labelled arachidonic acid, previously incorporated into the membranes, showed that part of the radioactivity released from the microsomal fraction into the incubation medium entered the dialysis tube and was recovered bound to the constituents of the microsomal fractions of the target system. These results indicate that during the course of the peroxidation of liver microsomal lipids toxic products are formed that are able to induce pathological effects at distant loci.

Animals↗
PubMed1999

The influence of organic peroxides on platelet aggregation and sensitivity to nitric oxide.

The effects of oxidative stress, induced by water-soluble and lipid peroxides, on platelet reactivity and platelet sensitivity to nitric oxide were investigated. Hydrogen peroxide and cumene hydroperoxide potentiated thrombin-induced platelet aggregation. In contrast, 15(S)-hydroperoxyeicosatetraenoic acid had no such effect, while 12(S)-hydroperoxyeicosatetraenoic acid inhibited platelet reactivity. All of the peroxides tested were found to decrease platelet sensitivity to nitric oxide, although the mechanisms by which the various peroxides altered platelet sensitivity to nitric oxide were different. The water-soluble peroxides opposed the actions of nitric oxide without affecting cyclic GMP levels, while 15(S)-hydroperoxyeicosatetraenoic acid caused a significant reduction in the concentration of cyclic GMP formed in response to NO. The data from this study demonstrate that water-soluble and lipid peroxides both affect platelet reactivity and regulation, but by different mechanisms. Thus, caution should be exercised when selecting peroxides to be used as models of oxidative stress.

Journal Article↗