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PubMed1981

Metabolic inhibition of Peptostreptococcus anaerobius decreases the bactericidal effect of hydrogen peroxide.

Peptostreptococcus anaerobius VPI 4330-1 was tested under various conditions for examination of the bactericidal effect of hydrogen peroxide. The cells were most rapidly killed by hydrogen peroxide when they were in the exponential-growth phase. Cooling or starving the cells decreased the bactericidal effect of hydrogen peroxide. The ionophore nigericin and the metal ion chelating agent 2,2'-bipyridine stopped macromolecular syntheses and greatly decreased the bactericidal effect of hydrogen peroxide. The ionophore valinomycin and the glycolytic inhibitor iodoacetate also stopped the syntheses of the macromolecules but only slightly decreased the bactericidal effect of hydrogen peroxide. Novobiocin, an inhibitor of deoxyribonucleic acid gyrase, and chloramphenicol, an inhibitor of protein synthesis, were not able to decrease the bactericidal effect of hydrogen peroxide. These findings implicate metal ions and an active metabolism of the organism in the bactericidal effect of hydrogen peroxide.

Antimetabolites↗
PubMed1978

Hydrogen peroxide release by rat alveolar macrophages: comparison with blood neutrophils.

Hydrogen peroxide release was examined using biochemical and cytochemical techniques in rat alveolar macrophages, at rest and during phagocytosis, and compared with rat blood neutrophils. Using biochemical techniques, alveolar macrophages released small amounts of hydrogen peroxide at rest, and no increase was observed after challenge with opsonized and nonopsonized zymosan particles at several particle-cell ratios (1:1 to 1:1,000). Neutrophils released similar quantities of hydrogen peroxide at rest but showed a 12-fold increase in hydrogen peroxide release following exposure to opsonized zymosan particles. Using cytochemical techniques to localize sites of hydrogen peroxide release, resting neutrophils showed little deposition of reaction product at the cell surface and occasional deposits in endocytotic vesicles. After exposure to latex particles, a dense reaction product was observed between the particle and the cell membrane, indicating significant increases in hydrogen peroxide release at the sites of particle contact with the neutrophil. The resting macrophage displayed a light, uniform precipitation of cerium over the cell surface and lining intracellular channels and endocytotic vesicles and vacuoles. Following particle exposure, there was no significant difference in the density or distribution of reaction product. These findings, together with previous studies of oxidative metabolism, suggest that alveolar macrophages do not release increased quantities of hydrogen peroxide during phagocytosis. In contrast to neutrophils, oxidative-dependent metabolic pathways may not be of primary importance for microbial killing by alveolar macrophages.

Animals↗
PubMed1988

Potential for free radical-induced lipid peroxidation as a cause of endothelial cell injury in Rocky Mountain spotted fever.

Cells infected by Rickettsia rickettsii, the causative agent of Rocky Mountain spotted fever, display unusual intracellular morphological changes characterized by dilatation of the membranes of the endoplasmic reticulum and outer nuclear envelope. These changes are consistent with those that might be expected to occur following peroxidation of membrane lipids initiated by oxygen radical species, such as the hydroxyl radical or a variety of organic radicals. Using a fluorescent probe, we have found significantly increased levels of peroxides in human endothelial cells infected by R. rickettsii. Studies with desferrioxamine, an iron chelator effective in preventing formation of the hydroxyl radical from hydrogen peroxide and the superoxide free radical, reduced peroxide levels in infected cells to those found in uninfected cells. This observation suggests that the increased peroxides in infected cells may be lipid peroxides, degradation products of free radical attack on polyenoic fatty acids. The potential for lipid peroxidation as an important mechanism in endothelial cell injury caused by R. rickettsii is discussed.

Deferoxamine↗
PubMed1994

Variation in hydrogen peroxide sensitivity between different strains of Neisseria gonorrhoeae is dependent on factors in addition to catalase activity.

Catalase, which catalyzes the reduction of hydrogen peroxide to oxygen and water, is considered the primary defense of Neisseria gonorrhoeae against exogenous hydrogen peroxide. Recent reports have demonstrated drastically different sensitivities of the organism to hydrogen peroxide ranging from greater than 80% survival after challenge with 30 mM hydrogen peroxide to less than 0.001% survival after challenge with 10 mM hydrogen peroxide. In this study, we have examined the hydrogen peroxide sensitivities of six clinical gonococcal isolates. The study demonstrates that the variations in gonococcal hydrogen peroxide sensitivities previously reported can be attributed to (i) differences in experimental methods employed or (ii) variation among different gonococcal strains. All of the gonococcal isolates examined generated similar concentrations of catalase, implying that the differences in the H2O2 sensitivity observed may depend on factors in addition to catalase.

Catalase↗
PubMed1982

Potentiation by L-cysteine of the bactericidal effect of hydrogen peroxide in Escherichia coli.

Under anaerobic conditions an exponentially growing culture of Escherichia coli K-12 was exposed to hydrogen peroxide in the presence of various compounds. Hydrogen peroxide (0.1 mM) together with 0.1 mM L-cysteine or L-cystine killed the organisms more rapidly than 10 mM hydrogen peroxide alone. The exposure of E. coli to hydrogen peroxide in the presence of L-cysteine inhibited some of the catalase. This inhibition, however, could not fully explain the 100-fold increase in hydrogen peroxide sensitivity of the organism in the presence of L-cysteine. Of other compounds tested only some thiols potentiated the bactericidal effect of hydrogen peroxide. These thiols were effective, however, only at concentrations significantly higher than 0.1 mM. The effect of L-cysteine and L-cystine could be annihilated by the metal ion chelating agent 2,2'-bipyridyl. DNA breakage in E. coli K-12 was demonstrated under conditions where the organisms were killed by hydrogen peroxide.

2,2'-Dipyridyl↗
PubMed1986

Repair response of Escherichia coli to hydrogen peroxide DNA damage.

The repair response of Escherichia coli to hydrogen peroxide-induced DNA damage was investigated in intact and toluene-treated cells. Cellular DNA was cleaved after treatment by hydrogen peroxide as analyzed by alkaline sucrose sedimentation. The incision step did not require ATP or magnesium and was not inhibited by N-ethylmaleimide (NEM). An ATP-independent, magnesium-dependent incorporation of nucleotides was seen after the exposure of cells to hydrogen peroxide. This DNA repair synthesis was not inhibited by the addition of NEM or dithiothreitol. In dnaB(Ts) strain CRT266, which is thermolabile for DNA replication, normal levels of DNA synthesis were found at the restrictive temperature (43 degrees C), showing that DNA replication was not necessary for this DNA synthesis. Density gradient analysis also indicated that hydrogen peroxide inhibited DNA replication and stimulated repair synthesis. The subsequent reformation step required magnesium, did not require ATP, and was not inhibited by NEM, in agreement with the synthesis requirements. This suggests that DNA polymerase I was involved in the repair step. Furthermore, a strain defective in DNA polymerase I was unable to reform its DNA after peroxide treatment. Chemical cleavage of the DNA was shown by incision of supercoiled DNA with hydrogen peroxide in the presence of a low concentration of ferric chloride. These findings suggest that hydrogen peroxide directly incises DNA, causing damage which is repaired by an incision repair pathway that requires DNA polymerase I.

Adenosine Triphosphate↗
PubMed1989

Multiple pathways for repair of hydrogen peroxide-induced DNA damage in Escherichia coli.

The repair response of Escherichia coli to hydrogen peroxide has been examined in mutants which show increased sensitivity to this agent. Four mutants were found to show increased in vivo sensitivity to hydrogen peroxide compared with wild type. These mutants, in order of increasing sensitivity, were recA, polC, xthA, and polA. The polA mutants were the most sensitive, implying that DNA polymerase I is required for any repair of hydrogen peroxide damage. Measurement of repair synthesis after hydrogen peroxide treatment demonstrated normal levels for recA mutants, a small amount for xthA mutants, and none for polA mutants. This is consistent with exonuclease III being required for part of the repair synthesis seen, while DNA polymerase I is strictly required for all repair synthesis. Sedimentation analysis of cellular DNA after hydrogen peroxide treatment showed that reformation was absent in xthA, polA, and polC(Ts) strains but normal in a recA cell line. By use of a lambda phage carrying a recA-lacZ fusion, we found hydrogen peroxide does not induce the recA promoter. Our findings indicate two pathways of repair for hydrogen peroxide-induced DNA damage. One of these pathways would utilize exonuclease III, DNA polymerase III, and DNA polymerase I, while the other would be DNA polymerase I dependent. The RecA protein seems to have little or no direct function in either repair pathway.

DNA Damage↗
PubMed1999

Campylobacter jejuni contains two fur homologs: characterization of iron-responsive regulation of peroxide stress defense genes by the PerR repressor.

Expression of the peroxide stress genes alkyl hydroperoxide reductase (ahpC) and catalase (katA) of the microaerophile Campylobacter jejuni is repressed by iron. Whereas iron repression in gram-negative bacteria is usually carried out by the Fur protein, previous work showed that this is not the case in C. jejuni, as these genes are still iron repressed in a C. jejuni fur mutant. An open reading frame encoding a Fur homolog (designated PerR for "peroxide stress regulator") was identified in the genome sequence of C. jejuni. The perR gene was disrupted by a kanamycin resistance cassette in C. jejuni wild-type and fur mutant strains. Subsequent characterization of the C. jejuni perR mutants showed derepressed expression of both AhpC and KatA at a much higher level than that obtained by iron limitation, suggesting that expression of these genes is controlled by other regulatory factors in addition to the iron level. Other iron-regulated proteins were not affected by the perR mutation. The fur perR double mutant showed derepressed expression of known iron-repressed genes. Further phenotypic analysis of the perR mutant, fur mutant, and the fur perR double mutant showed that the perR mutation made C. jejuni hyperresistant to peroxide stress caused by hydrogen peroxide and cumene hydroperoxide, a finding consistent with the high levels of KatA and AhpC expression, and showed that these enzymes were functional. Quantitative analysis of KatA expression showed that both the perR mutation and the fur mutation had profound effects on catalase activity, suggesting additional non-iron-dependent regulation of KatA and, by inference, AhpC. The PerR protein is a functional but nonhomologous substitution for the OxyR protein, which regulates peroxide stress genes in other gram-negative bacteria. Regulation of peroxide stress genes by a Fur homolog has recently been described for the gram-positive bacterium Bacillus subtilis. C. jejuni is the first gram-negative bacterium where non-OxyR regulation of peroxide stress genes has been described and characterized.

Amino Acid Sequence↗
PubMed2000

Recovery of hydrogen peroxide-sensitive culturable cells of Vibrio vulnificus gives the appearance of resuscitation from a viable but nonculturable state.

The viabilities of five strains of Vibrio vulnificus were evaluated during the storage of the organisms in sterile seawater at 5 degrees C. The number of CFU was measured by plate count methods on rich media. The total cell numbers were determined by direct microscopic count methods. The titer of CFU declined logarithmically to undetectable levels over a period of 2 to 3 weeks, while the total cell numbers were unchanged. Midway through each study, higher culturable cell counts began to be observed on plates containing catalase or sodium pyruvate; during the latter stages of the study, the plate counts on such media were up to 1,000-fold higher than those on unsupplemented plates. Because autoclaving is known to generate hydrogen peroxide in rich media, and because catalase and sodium pyruvate are known to eliminate hydrogen peroxide, it appears that the conditions of the experiments led to the selection of a hydrogen peroxide-sensitive culturable cell subpopulation. At the time of the final stage of the decline in viability of each culture, hydrogen peroxide-sensitive cells were the only culturable cells present. Warming samples of the cultures to room temperature led to the growth of these residual culturable cells, utilizing nutrients provided by the nonculturable cells. The cells that grew recovered hydrogen peroxide resistance. When mixtures of culturable and nonculturable cells were diluted to the point where only nonculturable cells were present, or when the hydrogen peroxide-sensitive culturable cells had declined to undetectable levels, warming had no effect; no culturable cells were recovered. Warming has been reported to "resuscitate" nonculturable cells. Recognition of the existence of hydrogen peroxide-sensitive culturable cell populations, as well as their ability to grow to high levels in the warmed seawater microcosms, leads instead to the conclusion that while warming permits culturable cells to grow, it has no effect on nonculturable cells.

Culture Media↗
PubMed2003

The global transcriptional response of Bacillus subtilis to peroxide stress is coordinated by three transcription factors.

Bacillus subtilis exhibits a complex adaptive response to low levels of peroxides. We used global transcriptional profiling to monitor the magnitude and kinetics of changes in the mRNA population after exposure to either hydrogen peroxide (H(2)O(2)) or tert-butyl peroxide (t-buOOH). The peroxide stimulons could be largely accounted for by three regulons controlled by the PerR, sigma(B), and OhrR transcription factors. Three members of the PerR regulon (katA, mrgA, and zosA) were strongly induced by H(2)O(2) and weakly induced by t-buOOH. The remaining members of the PerR regulon were only modestly up-regulated by peroxide treatment. Overall, the magnitude of peroxide induction of PerR regulon genes corresponded well with the extent of derepression in a perR mutant strain. The sigma(B) regulon was activated by 58 micro M H(2)O(2) but not by 8 micro M H(2)O(2) and was strongly activated by either t-buOOH or, in a control experiment, tert-butyl alcohol. Apart from the sigma(B) regulon there was a single gene, ohrA, that was strongly and rapidly induced by t-buOOH exposure. This gene, controlled by the peroxide-sensing repressor OhrR, was not induced by any of the other conditions tested.

Bacillus subtilis↗
PubMed1993

Role of active oxygen, lipid peroxidation, and antioxidants in the pathogenesis of gastric mucosal injury induced by indomethacin in rats.

The roles of active oxygen, lipid peroxidation, and the antioxidative defence mechanism in gastric mucosal injury induced by treatment with indomethacin in rats were investigated. The total area of gastric erosions and concentration of lipid peroxides in the gastric mucosa increased with time after administration of indomethacin (20 mg/kg, orally). The alpha-tocopherol:total cholesterol ratio in serum was significantly decreased and the activity of glutathione peroxidase, an important enzyme to scavenger of lipid peroxides, was inhibited by the administration of indomethacin. Treatments with superoxide dismutase and catalase inhibited the increases in gastric mucosal erosions and lipid peroxides in the gastric mucosa, and the reduction of serum alpha-tocopherol. Treatment with these scavengers did not improve the decreased glutathione peroxidase activity. These findings suggest that active oxygen species and lipid peroxidation play an important part in the pathogenesis of gastric mucosal injury induced by indomethacin, and that the decreased glutathione peroxidase activity aggravated the injury due to accelerated accumulation of hydrogen peroxide and lipid peroxides in the gastric mucosal cell.

Animals↗
PubMed1995

Effects of peroxide and superoxide on coronary artery: ANG II response and sarcoplasmic reticulum Ca2+ pump.

The sarcoplasmic reticulum (SR) Ca2+ pump in membranes isolated from arterial smooth muscle is damaged by reactive oxygen species (ROS). Because angiotensin II (ANG II) contracts arterial smooth muscle by mobilizing intracellular Ca2+ concentrations ([Ca2+])i, we determined the effects of ROS pretreatment on ANG II-induced contractions in coronary artery rings and [Ca2+]i transients in smooth muscle cells (SMC) cultured from them. This experimental design eliminates direct ROS interference in assay solutions, thus monitoring only the tissue damage. Pretreating the arteries with peroxide inhibited the ANG II contractions with the concentration for half-maximal activation (K0.5) = 74 +/- 5 microM. Peroxide (250 microM) inhibited the contractions to ANG II and cyclopiazonic acid (CPA, SR Ca(2+)-pump inhibitor) by 78.3 +/- 5.1 and 67.4 +/- 6.3%, respectively, but did not significantly affect the contractions by 60 mM KCl. Pretreating SMC with peroxide inhibited the ANG II-induced increase in [Ca2+]i with K0.5 = 24 +/- 3 microM for peroxide. Peroxide (100 microM) inhibited the increase in [Ca2+]i in response to ANG II and CPA by 78.9 +/- 5.1 and 38.3 +/- 4.9%, respectively. The SR Ca(2+)-pump activity was also measured as the Ca(2+)-dependent formation of 115-kDa acylphosphate. Pretreating SMC with 100 microM peroxide inhibited the acylphosphate levels by 36.3 +/- 3.2%. Peroxide (100 microM) pretreatment of SMC did not significantly affect their ANG II binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Acylation↗
PubMed1993

Effect of dietary lipid peroxides on metabolism of serum chylomicrons in rats.

We have found that in rats the peroxide content of chylomicrons (CM) is determined by the lipid peroxide concentration in the diet, indicating that dietary lipid peroxides are incorporated into the lymph CM. Moreover, these incorporated lipid peroxides influence the normal CM metabolism. When radiolabeled CM were injected into rats, there was no difference in the initial plasma removal between CM prepared from oil with low peroxide content (control CM) and CM prepared from oil with high peroxide content (oxidized CM). However, the tissue distribution of the labels indicated that the hepatic uptake of CM decreased with increasing lipid peroxide content of CM. At 10 min after injection of CM, liver uptake of cholesterol label was 48.39 +/- 3.08% for control CM and 31.41 +/- 10.73% for oxidized CM. Vitamin E enrichment of control CM increased their hepatic uptake to 61.07 +/- 0.83%. Additionally, binding of oxidized CM to the heart endothelium increased from 2.55 to 3.60% compared with binding of control CM. When the hydrolysis of control and oxidized CM by endothelial lipoprotein lipase (LPL) was tested in a heart perfusion system, we found that after 30 min, 56.51 +/- 5.81% of control and 76.82 +/- 1.75% of oxidized CM were not hydrolyzed and remained in the perfusate. Thus our results indicate that the altered metabolism of oxidized CM may be related to a reduced hydrolysis rate by endothelial LPL.

Animals↗
PubMed1998

Increased lipid peroxidation of erythrocytes in blood stored in polyvinyl chloride blood storage bags plasticized with di-[2-ethyl hexyl] phthalate and effect of antioxidants.

BACKGROUND AND OBJECTIVES: Previous work in this laboratory has shown significant decrease in vitamin E in erythrocytes in blood stored in polyvinyl chloride (PVC) bags plasticized with di-[2-ethyl hexyl] phthalate (DEHP), and in erythrocytes incubated in vitro with DEHP. Since vitamin E is a major antioxidant, a study was carried out to find out whether this decrease observed in vitamin E has an effect on lipid peroxidation in blood stored in DEHP-plasticized PVC blood bags. MATERIALS AND METHODS: Blood was collected in Penpol blood storage bags (which is a DEHP-plasticized PVC bag) and parameters of lipid peroxidation, i.e. activity of superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione reductase, concentration of malondialdehyde (MDA), conjugated dienes, hydroperoxides, glutathione and vitamin E studied in erythrocytes after various periods of storage as compared to glass bottles. Erythrocytes were also incubated in vitro with DEHP with and without vitamin E, and changes in lipid peroxidation studied. RESULTS: Blood stored in Penpol bags showed increased lipid peroxidation in erythrocytes as compared to that stored in glass bottles, as is evident from a greater increase in MDA and a greater decrease in glutathione and a significant decrease in vitamin E. The addition of vitamin E decreased the formation of MDA and conjugated dienes and prevented the decrease in vitamin E. However in spite of increased lipid peroxidation in the presence of DEHP, the release of K+ and hemoglobin from erythrocytes was lower. When there was an increase in DEHP taken up by erythrocytes, there was a corresponding decrease in vitamin E. More important, whenever there was an increase in vitamin E in erythrocytes (when RBCs in the presence of DEHP were incubated with vitamin E), there was a progressive decrease in DEHP. CONCLUSION: DEHP caused increased lipid peroxidation in erythrocytes. At the same time, it decreased the release of K+ and hemoglobin from erythrocytes. It is possible that the stabilizing effect of DEHP on the erythrocyte membrane may offset the detrimental effects of the increased lipid peroxidation it causes.

Adult↗
PubMedDate not supplied

Lipid peroxidation as additional marker in patients with colorectal cancer. Results of a preliminary study.

BACKGROUND AND AIMS: Up to now, various tumor markers have been proposed for the detection of the onset of malignant cell transformation or the better follow-up of cancer patients. The aim of the present study is to investigate the diagnostic value of systemic lipid peroxidation as an additional evaluative tool in the follow-up of surgical patients with colorectal cancer in combination to the clinically routine tumor markers carcinoembryonic antigen (CEA) and carcinoantigen 19-9 (CA 19-9). PATIENTS AND METHODS: 36 patients with a colorectal carcinoma were included in this study. Blood samples were collected 1 day prior to the operation, 10 days and 1 year after the operation. Oxygen free radical mediated lipid peroxidation was determined by measurement of thiobarbituric acid-reactive substances in the same serum that were used for the determination of tumor markers. RESULTS: Compared to control values, a highly significant increase of lipid peroxidation was found in the serum of all colorectal carcinoma patients up to the first 10 postoperative days. Differentiation of the patients, according to the T-stage, showed a marked and more obvious tendency towards higher serum lipid peroxides with increased tumor stage when compared to the conventional tumor markers. One year postoperatively the serum levels of lipid peroxidation returned to nearly normal values. Also the conventional tumor markers CEA and CA 19-9 showed a relative rise in the levels with the respective tumor stage, but differences were only statistically significant in the highest T-categories. CONCLUSION: After curative resection of the tumor, the level of systemic lipid peroxides decreases to normal values. We conclude from these results that the tumor is the primary cause of the increased systemic lipid peroxides.

Adult↗
PubMed1995

Modification of cisplatin-induced renal p-aminohippurate uptake alteration and lipid peroxidation by thiols, Ginkgo biloba extract, deferoxamine and torbafylline.

To determine whether inhibition of lipid peroxidation modifies cisplatin-induced changes of renal p-aminohippurate (PAH) uptake, we examined the effects of various radical scavengers and torbafylline on cisplatin-induced lipid peroxidation and PAH accumulation changes in rat renal cortical slices. Renal cortical slices were incubated with different cisplatin concentrations (0.3, 0.6, 1.0 mg/ml) in the presence of either glutathione, N-acetylcysteine, the iron chelator deferoxamine, Ginkgo biloba extract or the xanthine derivate torbafylline. Lipid peroxidation monitored as the production of malondialdehyde (MDA) was stimulated by increasing cisplatin concentrations in a dose-related manner. At a cisplatin concentration of 1.0 mg/ml, MDA production was twofold compared to controls (0.69 +/- 0.06 vs. 1.36 +/- 0.07 nmol/mg; p < 0.05). In turn, cisplatin decreased PAH uptake of kidney slices dose-dependently from 13.3 +/- 1.3 to 2.6 +/- 0.2 (p < 0.01). All agents tested inhibited cisplatin-induced lipid peroxidation; however, at a cisplatin concentration of 1.0 mg/ml, none of them prevented the decline of cisplatin-induced PAH uptake. Of the agents tested, deferoxamine proved to be the most effective antioxidant, completely inhibiting cisplatin-induced lipid peroxidation but in contrast preventing the decrease in PAH uptake only at a cisplatin concentration of 0.3 mg/ml. No strict association between lipid peroxidation and decline of PAH uptake was found, suggesting that lipid peroxidation may only in part participate in cisplatin-induced alterations of PAH uptake.

Acetylcysteine↗
PubMed1997

Copper ions promote peroxidation of low density lipoprotein lipid by binding to histidine residues of apolipoprotein B100, but they are reduced at other sites on LDL.

Oxidized LDL is implicated in the pathogenesis of atherosclerosis. A widely studied model for oxidation of the lipid in LDL involves Cu2+. Recent studies suggest that Cu2+ may be reduced to Cu1+ by alpha-tocopherol to initiate LDL lipid peroxidation. LDL demonstrates binding sites for Cu2-, but the nature of these binding sites, as well their role in promoting Cu2+ reduction and lipid peroxidation, has not been established. In the current studies, we used diethylpyrocarbonate (DEPC) to modify the histidine residues of apolipoprotein B100, the major protein in LDL. First, we demonstrated that histidine residues were preferentially modified by DEPC under our experimental conditions. Then we monitored the kinetics of Cu(2+)-promoted oxidation of LDL and DEPC-modified LDL. In both cases, the progress curve of lipid peroxidation exhibited a lag phase and a propagation phase. However, when LDL was modified with DEPC, the length of the lag phase was prolonged whereas the rate of lipid peroxidation during the propagation phase was lower. Studies with LDL oxidized by 2,2'-azobis (2-amidinopropane) hydrochloride and phosphatidylcholine liposomes oxidized with hydroxyl radical established that DEPC was not acting simply as a nonspecific inhibitor of lipid peroxidation. DEPC treatment of LDL almost completely inhibited its ability to bind Cu2+. These observations suggest that peroxidation of the lipids in LDL can proceed with normal kinetics only when Cu2+ binds preferentially to sites on apolipoprotein B100 that contain histidine residues. We also compared the kinetics of Cu2+ reduction in the absence and presence of DEPC. There was no effect of DEPC modification on either the rate or extent of Cu2+ reduction by LDL. Therefore LDL is likely to contain a second class of binding sites for Cu2+ that does not involve histidine residues. Thus, LDL appears to contain at least two classes of Cu(2+)-binding sites: histidine containing sites, which are responsible in part for promoting lipid peroxidation during the propagation phase, and sites at which Cu2+ is reduced without binding to histidine.

Antioxidants↗
PubMed1995

Endotoxin-induced hydrogen peroxide production in intact pulmonary circulation of rat.

Although the importance of free oxygen radical has been reported in acute lung injury, the direct evidence in vivo model was lacking. We report a new method, which for the first time allows direct detection of hydrogen peroxide in the intact rat pulmonary microcirculation. We used the computer image-analyzing system and 2',7'-dichlorofluorescin diacetate for the marker of hydrogen peroxide production in vivo. A rat sepsis model was produced by continuous infusion of endotoxin for 30, 60, and 120 min. Hydrogen peroxide production in the pulmonary microcirculation of the sepsis rat was higher than in the control rat at each time point (p < 0.01) and increased time-dependently (p < 0.01). Catalase (5,000 U/kg) almost completely inhibited the hydrogen peroxide production in the sepsis rat (p < 0.01). In high-power view, hydrogen peroxide was detected in granulocytes that adhered to the capillaries and endothelial cells that were adjoining adherent granulocytes. These observations suggest that hydrogen peroxide in the endothelium was diffused from granulocytes. In this study, we demonstrated direct evidence of hydrogen peroxide production from adherent granulocytes in intact rat lung treated with endotoxin. We conclude that endotoxin causes the granulocyte adhesion and oxidative stress to the endothelium due to adherent granulocytes within 30 min in the pulmonary microcirculation.

Animals↗