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Lipid Hydroperoxides (lipid + hydroperoxide)
Selected AbstractsShort-term antioxidant supplementation reduces oxidative stress in elderly patients with type 2 diabetes mellitus,a pilot studyPRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 7 2002SL Nuttall PhD Research Fellow Abstract Aims The aim of this pilot study was to determine what dose of which antioxidants might be studied in clinical trials by assessing the impact of vitamin (C and E) supplementation on markers of oxidative stress and LDL subfractions in patients with type 2 diabetes mellitus. Methods Nine elderly patients with type 2 diabetes took a moderate dose combination of vitamins C (500 mg) and E (400 IU) for 4 weeks. Following a 4 week washout, the patients had a further 4 weeks of supplementation with a higher dose combination of vitamins C (1000 mg) and E (800 IU). Blood was sampled pre- and post-supplementation for vitamin E by high-performance liquid chromatography (HPLC), total antioxidant capacity by enhanced chemiluminescence, total cholesterol and lipid hydroperoxides by colour spectrophotometry and LDL subfraction profile by disc polyacrylamide gel electrophoresis. Results Vitamin E was increased, after the moderate dose combination (59.8 ± 6 versus 36.4 ± 4 µmol/L, p < 0.001) and increased further by the higher dose (72.7 ± 11 versus 30.8 ± 5 µmol/L, p < 0.001). Total antioxidant capacity was significantly increased above baseline after both doses (508.2 ± 33 versus 436.4 ± 31, p < 0.01 (moderate); 519.3 ± 48 versus 440.8 ± 34 µmol/L trolox eq., p < 0.01 (high)). Lipid hydroperoxides were reduced more after the moderate dose combination than after the high dose (6.1 ± 1 versus 12.1 ± 2, p < 0.01; 8.0 ± 1 versus 11.6 ± 1 µmol/L, p < 0.05). LDL subfraction score showed a non-significant reduction after both periods of supplementation. Conclusions This study has demonstrated that supplementation with modest doses of the antioxidant vitamins C and E can significantly increase antioxidant defences and reduce oxidative damage in elderly patients with type 2 diabetes. Copyright © 2002 John Wiley & Sons, Ltd. [source] Arachidonic acid-mediated cooxidation of all- trans -retinoic acid in microsomal fractions from human liverBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2000Louise Nadin The quantitative importance of prostaglandin H synthase (PGHS)-mediated cooxidation of all- trans -retinoic acid (ATRA) was evaluated in human liver microsomes (n=17) in relation to CYP-dependent ATRA 4-hydroxylation. Observed rates of ATRA cooxidation (4.6,20 pmol mg protein,1 min,1) and 4-hydroxylation (8.7,45 pmol mg protein,1 min,1) were quantitatively similar and exhibited similar individual variation (4 and 5 fold, respectively). From kinetic studies cooxidation was an efficient process in human hepatic microsomes (VmaxKm,1=0.25) compared with NADPH- and NADH-mediated 4-hydroxylation by CYP (VmaxKm,1=0.14 and 0.02, respectively). The capacity of lipid hydroperoxide metabolites of arachidonic acid to mediate ATRA oxidation was established directly, but downstream products (D, E, F and I-series prostaglandins) were inactive. cDNA-expressed CYPs supported ATRA oxidation by lipid hydroperoxides. Whereas CYPs 2C8, 2C9 and 3A4, but not CYPs 1A2 or 2E1, were effective catalysts of the NADPH-mediated reaction, cooxidation supported by 15(S)-hydroperoxyeicosatetraenoic acid was mediated by all five CYPs. The cooxidation reaction in human hepatic microsomes was inhibited by the CYP inhibitor miconazole. These findings indicate that ATRA oxidation is quantitatively significant in human liver. Lipid hydroperoxides generated by intracellular enzymes such as prostaglandin synthase and lipoxygenases are sources of activated oxygen for CYP-mediated deactivation of ATRA to polar products. British Journal of Pharmacology (2000) 131, 851,857; doi:10.1038/sj.bjp.0703579 [source] Mechanisms and Factors for Edible Oil OxidationCOMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETY, Issue 4 2006Eunok Choe ABSTRACT:,Edible oil is oxidized during processing and storage via autoxidation and photosensitized oxidation, in which triplet oxygen (3O2) and singlet oxygen (1O2) react with the oil, respectively. Autoxidation of oils requires radical forms of acylglycerols, whereas photosensitized oxidation does not require lipid radicals since 1O2 reacts directly with double bonds. Lipid hydroperoxides formed by 3O2 are conjugated dienes, whereas 1O2 produces both conjugated and nonconjugated dienes. The hydroperoxides are decomposed to produce off-flavor compounds and the oil quality decreases. Autoxidation of oil is accelerated by the presence of free fatty acids, mono- and diacylglycerols, metals such as iron, and thermally oxidized compounds. Chlorophylls and phenolic compounds decrease the autoxidation of oil in the dark, and carotenoids, tocopherols, and phospholipids demonstrate both antioxidant and prooxidant activity depending on the oil system. In photosensitized oxidation chlorophyll acts as a photosensitizer for the formation of 1O2; however, carotenoids and tocopherols decrease the oxidation through 1O2 quenching. Temperature, light, oxygen concentration, oil processing, and fatty acid composition also affect the oxidative stability of edible oil. [source] Serum paraoxonase and arylesterase activities for the evaluation of patients with chronic hepatitisINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 7 2008M. Aslan Summary The sensitivity of standard biochemical tests for liver function is low and insufficient for a reliable determination of the presence or absence of liver disease. The aim of the present study was to investigate serum paraoxonase and arylesterase activities and lipid hydroperoxide (LOOH) levels, and to find out that whether the measurement of serum paraoxonase and arylesterase activities would be useful as an index of liver function status in chronic hepatitis (CH). Fourty-four patients with CH (24 CHB and 20 CHC) and 38 controls were enrolled. Serum paraoxonase and arylesterase activities were detected spectrophotometrically. LOOH levels were measured by the FOX-2 assay. Serum paraoxonase and arylesterase activities were significantly lower in patients with CH than controls (p < 0.001 for both), while LOOH levels were significantly higher (p < 0.001). Paraoxonase and arylesterase activities were inversely correlated with LOOH levels (r = ,0.394, p < 0.05; r =,0.362, p < 0.05, respectively). Fibrosis scores of CH patients were significantly correlated with paraoxonase and arylesterase activities and LOOH levels (r =,0.276, p < 0.05; r = ,0.583, p < 0.001 and r = 0.562, p < 0.001, respectively). Our results indicated that decrease in the activities paraoxonase and arylesterase may play a role in the pathogenesis of CH. In addition, serum paraoxonase and arylesterase activities measurement may add a significant contribution to the liver function tests. [source] Melatonin protects kidney grafts from ischemia/reperfusion injury through inhibition of NF-kB and apoptosis after experimental kidney transplantationJOURNAL OF PINEAL RESEARCH, Issue 4 2009Zhanqing Li Abstract:, Free radicals are involved in pathophysiology of ischemia/reperfusion injury (IRI). Melatonin is a potent scavenger of reactive oxygen and nitrogen species. Thus, this study was designed to elucidate its effects in a model of rat kidney transplantation. Twenty Lewis rats were randomly divided into 2 groups (n = 10 animals each). Melatonin (50 mg/kg BW) dissolved in 5 mL milk was given to one group via gavage 2 hr before left donor nephrectomy. Controls were given the same volume of milk only. Kidney grafts were then transplanted into bilaterally nephrectomized syngeneic recipients after 24 hr of cold storage in Histidine,Tryptophan,Ketoglutarate solution. Both graft function and injury were assessed after transplantation through serum levels of blood urea nitrogen (BUN), creatinine, transaminases, and lactate dehydrogenase (LDH). Biopsies were taken to evaluate tubular damage, the enzymatic activity of superoxide dismutase (SOD) and lipid hydroperoxide (LPO), and the expression of NF-kBp65, inducible nitric oxide synthase (iNOS), caspase-3 as indices of oxidative stress, necrosis, and apoptosis, respectively. Melatonin improved survival (P < 0.01) while decreasing BUN, creatinine, transaminases, and LDH values up to 39,71% (P < 0.05). Melatonin significantly reduced the histological index for tubular damage, induced tissue enzymatic activity of SOD while reducing LPO. At the same time, melatonin down-regulated the expression of NF-kBp65, iNOS, and caspase-3. In conclusion, donor preconditioning with melatonin protected kidney donor grafts from IRI-induced renal dysfunction and tubular injury most likely through its anti-oxidative, anti-apoptotic and NF-kB inhibitory capacity. [source] Citrus abscission and Arabidopsis plant decline in response to 5-chloro-3-methyl-4-nitro-1H -pyrazole are mediated by lipid signallingPLANT CELL & ENVIRONMENT, Issue 11 2005FERNANDO ALFEREZ ABSTRACT The compound 5-chloro-3-methyl-4-nitro-1H -pyrazole (CMNP) is a pyrazole-derivative that induces abscission selectively in mature citrus (Citrus sinensis) fruit when applied to the canopy and has herbicidal activity on plants when applied to roots. Despite the favourable efficacy of this compound, the mode of action remains unknown. To gain information about the mode of action of CMNP, the effect of application to mature citrus fruit and Arabidopsis thaliana roots was explored. Peel contact was essential for mature fruit abscission in citrus, whereas root drenching was essential for symptom development and plant decline in Arabidopsis. CMNP was identified as an uncoupler in isolated soybean (Glycine max) mitochondria and pea (Pisum sativum) chloroplasts and an inhibitor of alcohol dehydrogenase in citrus peel, but not an inhibitor of protoporphyrinogen IX oxidase. CMNP treatment reduced ATP content in citrus peel and Arabidopsis leaves. Phospholipase A2 (PLA2) and lipoxygenase (LOX) activities, and lipid hydroperoxide (LPO) levels increased in flavedo of citrus fruit peel and leaves of Arabidopsis plants treated with CMNP. An inhibitor of PLA2 activity, aristolochic acid (AT), reduced CMNP-induced increases in PLA2 and LOX activities and LPO levels in citrus flavedo and Arabidopsis leaves and greatly reduced abscission in citrus and delayed symptoms of plant decline in Arabidopsis. However, AT treatment failed to halt the reduction in ATP content. Reduction in ATP content preceded the increase in PLA2 and LOX activities, LPO content and the biological response. The results indicate a link between lipid signalling, abscission in citrus and herbicidal damage in Arabidopsis. [source] Determination of cellular redox status by stable isotope dilution liquid chromatography/mass spectrometry analysis of glutathione and glutathione disulfideRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 4 2008Peijuan Zhu Oxidation of glutathione (GSH) to glutathione disulfide (GSSG) occurs during cellular oxidative stress. The redox potential of the 2GSH/GSSG couple, which is determined by the Nernst equation, provides a means to assess cellular redox status. It is difficult to accurately quantify GSH and GSSG due to the ease with which GSH is oxidized to GSSG during sample preparation. To overcome this problem, a stable isotope dilution liquid chromatography/multiple reaction monitoring mass spectrometry (LC/MRM-MS) method has been developed using 4-fluoro-7-sulfamoylbenzofurazan (ABD-F) derivatization. ABD-F derivatization of the GSH thiol group was rapid, quantitative, and occurred at room temperature. The LC/MRM-MS method, which requires no sample clean-up, was validated within the calibration ranges of 5 to 400,nmol/mL in cell lysates for GSH and 0.5 to 40,nmol/mL in cell lysates for GSSG. Calibration curves prepared by adding known concentrations of GSH and GSSG to cell lysates were parallel to the standard curve prepared in buffers. GSH and GSSG concentrations were determined in two monocyte/macrophage RAW 267.4 cell lines with or without 15-LOX-1 expression (R15LO and RMock cells, respectively) after treatment with the bifunctional electrophile 4-oxo-2(E)-nonenal (ONE). R15LO cells synthesized much higher concentrations of the lipid hydroperoxide, 15(S)-hydroperoxyeicosatetraenoic acid (15-HPETE), which undergoes homolytic decomposition to ONE. GSH was depleted by ONE treatment in both RMock and R15LO cells, leading to significant increases in their redox potentials. However, R15LO cells had higher GSH concentrations (most likely through increased GSH biosynthesis) and had increased resistance to ONE-mediated GSH depletion than RMock cells. Consequently, R15LO cells had lower reduction potentials at all concentrations of ONE. GSSG concentrations were higher in R15LO cells after ONE treatment when compared with the ONE-treated RMock cells. This suggests that increased expression of 15(S)-HPETE modulates the activity of cellular GSH reductases or the transporters involved in removal of GSSG. Copyright © 2008 John Wiley & Sons, Ltd. [source] Antioxidative activity and ameliorative effects of memory impairment of sulfur-containing compounds in Allium speciesBIOFACTORS, Issue 2 2006Hiroyuki Nishimura Abstract The antioxidative activity and ameliorative effects on memory impairment by sulfur-containing compounds which occur in Allium vegetables such as onion and garlic were investigated. The antioxidative activities of S-alk(en)yl-L-cysteines and their sulfoxides, volatile alk(en)yl disulfides and trisulfides, and vinyldithiins were examined by using human low-density lipoprotein. It was elucidated that the alk(en)yl substituents and the number of sulfur atoms in the compounds were important for the antioxidative activities. To demonstrate the ameliorative effects on memory impairment, onion extract and synthesized di-n-propyl trisulfide were administered to senescence-accelerated mouse P8. The behavioral experiments showed that onion extract and di-n-propyl trisulfide had highly ameliorative effect of memory impairment. Furthermore, it was found that the hippocampus lipid hydroperoxide in senescence-accelerated mouse P8 was decreased by the administration of di-n-propyl trisulfide. These results suggest that di-n-propyl trisulfide contained in onion ameliorates memory impairment in SAMP8 mouse by its antioxidant effect. [source] Antioxidative activity of sulfur-containing compounds in Allium species for human LDL oxidation in vitroBIOFACTORS, Issue 1-4 2004Hiroyuki Nishimura Abstract Sulfur-containing compounds contributing to health promotion in Allium species are produced via enzymic and thermochemical reactions. Sulfur-containing amino acids and volatile organosulfur compounds were prepared for an antioxidative assay. The inhibitory activity of S-alk(en)yl-L-cysteines and their sulfoxides, volatile alk(en)yl disulfides and trisulfides, and vinyldithiins in Allium species against lipid hydroperoxide (LOOH) formation in human low-density lipoprotein (LDL) was examined. It was elucidated that the alk(en)yl substituents (methyl, propyl, and allyl) and the number of sulfur atoms in the compounds were important for the antioxidative activity. 3,4-Dihydro-3-vinyl-1,2-dithiin, which is produced by a thermochemical reaction of allyl 2-propenethiosulfinate, exhibited the highest antioxidative activity of human LDL among sulfur-containing compounds. [source] Effect of green tea catechins on oxidative DNA damage of hamster pancreas and liver induced by N-Nitrosobis(2-oxopropyl)amine and/or oxidized soybean oilBIOFACTORS, Issue 1-4 2004Fumiyo Takabayashi Abstract It has been indicated that high fat diet is a risk factor of the pancreatic cancer by epidemiological studies. We examined whether the oxidized soybean oil (ox-oil) express the synergistic effect on the formation of 8-ox O2,'-deoxyguanosine (8-oxodG) in nuclear DNA of hamster pancreas induced by N-Nitrosobis(2-oxopropyl)amine (BOP) and whether the green tea catechins (GTC) suppressed it. Ox-oil was prepared by air oxidation, and the content of lipid hydroperoxide was 6.22 mg/ml. Hamsters were administered 0.3,ml of ox-oil/day orally for 4 weeks before BOP treatment. GTC was given ad libitum as a 0.1% aqueous solution. Four hours after subcutaneous administration of BOP, hamsters were sacrificed, and the contents of 8-oxodG were measured in nuclear DNA of pancreas and liver. The 8-oxodG content in the pancreas was increased by BOP and/or ox-oil administration. However, it was not suppressed by an intake of GTC. In the liver, though the content of 8-oxodG was increased by ox-oil, it tended to suppress the rise of 8-oxodG by a GTC intake. These results suggested that the long term intake of ox-oil might have the possibility to induce carcinogenesis in hamster pancreas and liver, and an intake of GTC might have the beneficial effect on liver. [source] Lipid peroxidation and total antioxidant status in patients with breast cancerCELL BIOCHEMISTRY AND FUNCTION, Issue 4 2007Derya Erten, ener Abstract Oxidative stress is considered to be involved in the pathophysiology of all cancers. The aim of this study is to examine oxidative stress and antioxidant status in patients with breast cancer by evaluation of the serum levels of total antioxidant capacity (TAC) and lipid peroxidation products as malondialdehyde (MDA) and lipid hydroperoxide and to investigate the relationship between these parameters, oxidative stress and serum lipids and lipoproteins. In our study, serum TAC, MDA, lipid hydroperoxide, HDL-cholesterol, VLDL-cholesterol, LDL-cholesterol, total cholesterol, triacylglycerol (TAG), albumin and uric acid levels of 56-breast cancer patients in different clinical stages and 18 healthy women were determined. Significantly lower-levels of TAC were detected in patients with breast cancer in comparison to controls (2.01,±,0.01,mmol/l and 2.07,±,0.03,mmol/l, respectively, p,<,0.05). Serum MDA levels of the patients were higher compared to the controls (3.64,±,0.25,µM and 2.72,±,0.22,µM, respectively, p,<,0.05). No significant difference between lipid hydroperoxide levels of patients and controls was found (0.33,±,0.05,µM and 0.32,±,0.01,µM, respectively, p,>,0.05). These data show that lower TAC and higher MDA levels i.e. increased oxidative stress may be related to breast cancer. Copyright © 2006 John Wiley & Sons, Ltd. [source] Limiting light-induced lipid peroxidation and vitamin loss in infant parenteral nutrition by adding multivitamin preparations to IntralipidACTA PAEDIATRICA, Issue 3 2001KM Silvers Parenteral lipids are susceptible to light-induced peroxidation, particularly under phototherapy. Ascorbic acid is protective. The aim of this study was to investigate whether dark delivery tubing and/or coadministration of multivitamin preparations could prevent peroxidation of Intralipid without undue vitamin loss. In experiments carried out on the benchtop, lipid peroxidation occurred in ambient light and was more extensive under phototherapy. Dark tubing decreased peroxide formation, but only by about 65%. In simulated clinical conditions in which solutions were pumped through standard clear or dark minibore plastic tubing, Intralipid accumulated lipid peroxides as measured by the FOX assay (280 ,M) or as triglyceride hydroperoxides (52 ,M). Multivitamin preparations (MVIP or Soluvit/Vitlipid) inhibited peroxide formation almost completely, and were fully protective when used with dark tubing. There was loss of riboflavin (65% from Soluvit and 35% from MVIP) in clear tubing but this was decreased to 18% and 11%, respectively, in dark tubing. Ascorbate loss was 20% (MVIP) and 50% (Soluvit) and only slightly less in dark tubing. Ascorbate loss was also seen in the absence of Intralipid and is due to riboflavin-induced photo-oxidation. Conclusion: Multivitamin preparations protect Intralipid against light-induced formation of lipid hydroperoxides, and administering multivitamins with Intralipid via dark delivery tubing provides a practical way of preventing peroxidation of the lipid while limiting vitamin loss. This procedure should be considered for routine use as well as with phototherapy. [source] Ascorbic acid improves the antioxidant activity of European grape juices by improving the juices' ability to inhibit lipid peroxidation of human LDL in vitroINTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 7 2001Anne-Katrine Landbo Antioxidant activities of red and white European grape juices towards copper induced lipid oxidation of human low-density lipoproteins (LDL) were examined in vitro. LDL lipid peroxidation was assessed spectrophotometrically by monitoring the development of conjugated lipid hydroperoxides at 234 nm. Red grape juice concentrate inhibited lipid peroxidation of LDL by prolonging the lag phase by 2.7 times relative to a control when evaluated at a total phenolic concentration of 10 ,M gallic acid equivalents (GAE). Both red grape juices tested blocked lipid peroxidation of LDL at 20 ,M GAE. White grape juice exerted prooxidant activity at 5,20 ,M GAE. The antioxidant activity, inhibition of lipid peroxidation of LDL in vitro, was correlated with the juices' levels of total phenols (r > 0.98, P < 0.01), anthocyanins (r > 0.99, P < 0.01), flavan-3-ols (r > 0.97, P < 0.05), and hydroxybenzoates (r > 0.96, P < 0.05) when the phenolic composition of each grape juices was analysed by HPLC. 5 ,M ascorbic acid alone did not exert antioxidant activity towards LDL, but combinations of 5 ,M ascorbic acid with 5 ,M GAE juice phenols eliminated the prooxidant activity of white grape juice, and significantly improved the antioxidant activities of red grape juices. [source] Biological hydroperoxides and singlet molecular oxygen generationIUBMB LIFE, Issue 4-5 2007Sayuri Miyamoto Abstract The decomposition of lipid hydroperoxides (LOOH) into peroxyl radicals is a potential source of singlet molecular oxygen (1O2) in biological systems. Recently, we have clearly demonstrated the generation of 1O2 in the reaction of lipid hydroperoxides with biologically important oxidants such as metal ions, peroxynitrite and hypochlorous acid. The approach used to unequivocally demonstrate the generation of 1O2 in these reactions was the use of an isotopic labeled hydroperoxide, the 18O-labeled linoleic acid hydroperoxide, the detection of labeled compounds by HPLC coupled to tandem mass spectrometry (HPLC-MS/MS) and the direct spectroscopic detection and characterization of 1O2 light emission. Using this approach we have observed the formation of 18O-labeled 1O2 by chemical trapping of 1O2 with anthracene derivatives and detection of the corresponding labeled endoperoxide by HPLC-MS/MS. The generation of 1O2 was also demonstrated by direct spectral characterization of 1O2 monomol light emission in the near-infrared region (, = 1270 nm). In summary, our studies demonstrated that LOOH can originate 1O2. The experimental evidences indicate that 1O2 is generated at a yield close to 10% by the Russell mechanism, where a linear tetraoxide intermediate is formed in the combination of two peroxyl radicals. In addition to LOOH, other biological hydroperoxides, including hydroperoxides formed in proteins and nucleic acids, may also participate in reactions leading to the generation 1O2. This hypothesis is currently being investigated in our laboratory. [source] (,)Epigallocatechingallate protects the mitochondria against the deleterious effects of lipids, calcium and adenosine triphosphate in isoproterenol induced myocardial infarcted male Wistar ratsJOURNAL OF APPLIED TOXICOLOGY, Issue 8 2008P. T. Devika Abstract The present study was undertaken to evaluate the protective effect of (,)epigallocatechin gallate (EGCG) on mitochondrial lipids, lipid peroxides, Na+/K+ ATPase, calcium and adenosine triphosphate in isoproterenol (ISO) induced myocardial infarction in male Wistar rats. Rats were pretreated with EGCG (30 mg kg,1 body weight) orally using an intragastric tube daily for a period of 21 days. After that, ISO (100 mg kg,1 body weight) was subcutaneously injected to rats at intervals of 24 h for two days. ISO induced rats showed significant increase in the levels of cholesterol, triglycerides and free fatty acids with subsequent decrease in the levels of phospholipids in mitochondrial fraction of the heart. ISO induction also caused significant increase in lipid peroxidation products (thiobarbituric acid reactive substances and lipid hydroperoxides) and significant decrease in the activity of Na+/K+ ATPase in mitochondrial fraction of the heart. A significant increase in the levels of calcium and significant decrease in the levels of adenosine triphosphate were observed in ISO-induced mitochondrial heart. Prior treatment with EGCG (30 mg kg,1) significantly protected these alterations and maintained normal mitochondrial function. Thus, this study confirmed the protective effect of EGCG on mitochondria in experimentally induced cardiotoxicity in Wistar rats. Copyright © 2008 John Wiley & Sons, Ltd. [source] Biochemical and ultrastructural alterations in the rat ventral prostate due to repetitive alcohol drinkingJOURNAL OF APPLIED TOXICOLOGY, Issue 4 2007M. I. Díaz Gómez Abstract Previous studies showed that cytosolic and microsomal fractions from rat ventral prostate are able to biotransform ethanol to acetaldehyde and 1-hydroxyethyl radicals via xanthine oxidase and a non P450 dependent pathway respectively. Sprague Dawley male rats were fed with a Lieber and De Carli diet containing ethanol for 28 days and compared against adequately pair-fed controls. Prostate microsomal fractions were found to exhibit CYP2E1-mediated hydroxylase activity significantly lower than in the liver and it was induced by repetitive ethanol drinking. Ethanol drinking led to an increased susceptibility of prostatic lipids to oxidation, as detected by t-butylhydroperoxide-promoted chemiluminiscence emission and increased levels of lipid hydroperoxides (xylenol orange method). Ultrastructural alterations in the epithelial cells were observed. They consisted of marked condensation of chromatin around the perinuclear membrane, moderate dilatation of the endoplasmic reticulum and an increased number of epithelial cells undergoing apoptosis. The prostatic alcohol dehydrogenase activity of the stock rats was 4.84 times lower than that in the liver and aldehyde dehydrogenase activity in their microsomal, cytosolic and mitochondrial fractions was either not detectable or significantly less intense than in the liver. A single dose of ethanol led to significant acetaldehyde accumulation in the prostate. The results suggest that acetaldehyde accumulation in prostate tissue might result from both acetaldehyde produced in situ but also because of its low aldehyde dehydrogenase activity and its poor ability to metabolize acetaldehyde arriving via the blood. Acetaldehyde, 1-hydroxyethyl radical and the oxidative stress produced may lead to epithelial cell injury. Copyright © 2007 John Wiley & Sons, Ltd. [source] Antilipoperoxidative and antioxidant effects of S-allyl cysteine sulfoxide on isoproterenol-induced myocardial infarction in wistar ratsJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 4 2006T. Sangeetha Abstract Our study evaluates the preventive effect of S-allyl cysteine sulfoxide (SACS) on lipid peroxidative products and enzymic and nonenzymic antioxidants in isoproterenol (ISO) induced myocardial infarction in rats. The male Wistar rats were rendered myocardial infarction by ISO (150 mg kg,1, once a day for two days). The concentrations of thiobarbituric acid reactive substances and lipid hydroperoxides were increased in hearts from ISO-treated rats, whereas the content of enzymic and nonenzymic antioxidants were declined in rats administered ISO. Oral pretreatment with SACS (40 mg kg,1 and 80 mg kg,1 daily for a period of 35 days) significantly (p < 0.05) decreased the lipid peroxidative products and significantly (p < 0.05) increased antioxidants in ISO-induced rats. Oral administration of SACS (40 mg kg,1 and 80 mg kg,1) did not show any significant effect in normal rats. Thus, the present study shows that SACS exhibits antilipoperoxidative and antioxidant effects in experimental myocardial infarction. © 2006 Wiley Periodicals, Inc. J Biochem Mol Toxicol 20:167,173, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20132 [source] Lipid Oxidation in Poultry Döner Kebab: Pro-oxidative and Anti-oxidative FactorsJOURNAL OF FOOD SCIENCE, Issue 2 2003B. Kilic ABSTRACT: The effect of mechanically separated turkey (MST), ascorbate, and vacuum packaging on rates of lipid oxidation in chicken döner kebab during storage at 4 °C or -20 °C was investigated. MST and MST/ascor-bate accelerated lipid oxidation compared to control kebab. Ascorbate application and vacuum packaging inhibited lipid oxidation. The antioxidative effect of ascorbate in the absence of MST was converted to a pro-oxidative effect in the presence of MST. This suggests that the excess lipid hydroperoxides and iron complexes in MST were activated as lipid oxidation catalysts by ascorbate to overwhelm the ability of ascorbate to inhibit lipid oxidation at lower concentrations of hemoglobin, iron, and peroxides. [source] Dose-response efficacy of caraway (Carum carvi L.) on tissue lipid peroxidation and antioxidant profile in rat colon carcinogenesisJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2006Muthaiyan Kamaleeswari Colon cancer is a leading cause of cancer death and its prevention is of great interest throughout the world. This study was conducted to examine the efficacy of different doses of dietary caraway (Carum carvi L.) on tissue lipid peroxidation (LPO) and antioxidant profile in rat colon carcinogenesis. Wistar male rats were divided into 6 groups and were fed a modified pellet diet for the whole of 30 weeks. To induce colon cancer, rats were given a weekly subcutaneous injection of 1,2-dimethylhydrazine (DMH) at a dose of 20 mg kg,1 (based on body weight) for the first 15 weeks. Caraway was supplemented every day orally at doses of 30, 60 and 90 mg kg,1 for different groups of rats for the total period of 30 weeks. All rats were sacrificed at the end of 30 weeks, the colons were examined visually for masses and were subsequently evaluated histologically. The results showed diminished levels of intestinal, colonic and caecal LPO products, such as conjugated dienes (CD), lipid hydroperoxides (LOOH) and thiobarbituric acid reactive substances (TBARS) and also the antioxidants superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and glutathione reductase (GR) in DMH treated rats, which were significantly reversed (P < 0.05) on caraway supplementation. Moreover, enhanced activity of intestinal, colonic and caecal glutathione peroxidase (GPx), glutathione S-transferase (GST) and colonic ascorbic acid and ,-tocopherol levels were observed in carcinogen-treated rats, which were significantly (P < 0.05) reduced on caraway supplementation. Thus, our study showed that caraway supplementation at a dose of 60 mg kg,1 had a modulatory role on tissue LPO, antioxidant profile and prevented DMH-induced histopathological lesions in colon cancer rats. [source] Short-term antioxidant supplementation reduces oxidative stress in elderly patients with type 2 diabetes mellitus,a pilot studyPRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 7 2002SL Nuttall PhD Research Fellow Abstract Aims The aim of this pilot study was to determine what dose of which antioxidants might be studied in clinical trials by assessing the impact of vitamin (C and E) supplementation on markers of oxidative stress and LDL subfractions in patients with type 2 diabetes mellitus. Methods Nine elderly patients with type 2 diabetes took a moderate dose combination of vitamins C (500 mg) and E (400 IU) for 4 weeks. Following a 4 week washout, the patients had a further 4 weeks of supplementation with a higher dose combination of vitamins C (1000 mg) and E (800 IU). Blood was sampled pre- and post-supplementation for vitamin E by high-performance liquid chromatography (HPLC), total antioxidant capacity by enhanced chemiluminescence, total cholesterol and lipid hydroperoxides by colour spectrophotometry and LDL subfraction profile by disc polyacrylamide gel electrophoresis. Results Vitamin E was increased, after the moderate dose combination (59.8 ± 6 versus 36.4 ± 4 µmol/L, p < 0.001) and increased further by the higher dose (72.7 ± 11 versus 30.8 ± 5 µmol/L, p < 0.001). Total antioxidant capacity was significantly increased above baseline after both doses (508.2 ± 33 versus 436.4 ± 31, p < 0.01 (moderate); 519.3 ± 48 versus 440.8 ± 34 µmol/L trolox eq., p < 0.01 (high)). Lipid hydroperoxides were reduced more after the moderate dose combination than after the high dose (6.1 ± 1 versus 12.1 ± 2, p < 0.01; 8.0 ± 1 versus 11.6 ± 1 µmol/L, p < 0.05). LDL subfraction score showed a non-significant reduction after both periods of supplementation. Conclusions This study has demonstrated that supplementation with modest doses of the antioxidant vitamins C and E can significantly increase antioxidant defences and reduce oxidative damage in elderly patients with type 2 diabetes. Copyright © 2002 John Wiley & Sons, Ltd. [source] Altered free radical metabolism in acute mountain sickness: implications for dynamic cerebral autoregulation and blood,brain barrier functionTHE JOURNAL OF PHYSIOLOGY, Issue 1 2009D. M. Bailey We tested the hypothesis that dynamic cerebral autoregulation (CA) and blood,brain barrier (BBB) function would be compromised in acute mountain sickness (AMS) subsequent to a hypoxia-mediated alteration in systemic free radical metabolism. Eighteen male lowlanders were examined in normoxia (21% O2) and following 6 h passive exposure to hypoxia (12% O2). Blood flow velocity in the middle cerebral artery (MCAv) and mean arterial blood pressure (MAP) were measured for determination of CA following calculation of transfer function analysis and rate of regulation (RoR). Nine subjects developed clinical AMS (AMS+) and were more hypoxaemic relative to subjects without AMS (AMS,). A more marked increase in the venous concentration of the ascorbate radical (A,,), lipid hydroperoxides (LOOH) and increased susceptibility of low-density lipoprotein (LDL) to oxidation was observed during hypoxia in AMS+ (P < 0.05 versus AMS,). Despite a general decline in total nitric oxide (NO) in hypoxia (P < 0.05 versus normoxia), the normoxic baseline plasma and red blood cell (RBC) NO metabolite pool was lower in AMS+ with normalization observed during hypoxia (P < 0.05 versus AMS,). CA was selectively impaired in AMS+ as indicated both by an increase in the low-frequency (0.07,0.20Hz) transfer function gain and decrease in RoR (P < 0.05 versus AMS,). However, there was no evidence for cerebral hyper-perfusion, BBB disruption or neuronal,parenchymal damage as indicated by a lack of change in MCAv, S100, and neuron-specific enolase. In conclusion, these findings suggest that AMS is associated with altered redox homeostasis and disordered CA independent of barrier disruption. [source] 18O-Labeled lipid hydroperoxides and HPLC coupled to mass spectrometry as valuable tools for studying the generation of singlet oxygen in biological systemBIOFACTORS, Issue 1-4 2004Sayuri Miyamoto Abstract Decomposition of lipid hydroperoxides (LOOH) is known to generate toxic products capable to induce tissue injury. We have recently confirmed that decomposition of LOOH into peroxyl radicals is a potential source of singlet oxygen (1O2) in biological system. Using 18O-labeled linoleic acid hydroperoxide (LA18O18OH) in the presence of Ce4+ or Fe+2, we observed the formation of 18O-labeled 1O2 (18[1O2]) by chemical trapping of 1O2 with 9,10-diphenylanthracene (DPA) and detecting the corresponding 18O-labeled DPA endoperoxide (DPA18O18O) by HPLC coupled to tandem mass spectrometry (HPLC-MS/MS). 18O-Labeled alcohol and ketone were also detected providing further evidence for the generation of 1O2by the Russell mechanism. Similarly the reaction of LA18O18OH with peroxynitrite also generated18[1O2]. In conclusion, these results indicates that the use of 18O-labeled LOOH associated with HPLC-MS/MS can be an useful tool to clarify mechanistic features involved in the reaction of LOOH in biological media. [source] Arachidonic acid-mediated cooxidation of all- trans -retinoic acid in microsomal fractions from human liverBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2000Louise Nadin The quantitative importance of prostaglandin H synthase (PGHS)-mediated cooxidation of all- trans -retinoic acid (ATRA) was evaluated in human liver microsomes (n=17) in relation to CYP-dependent ATRA 4-hydroxylation. Observed rates of ATRA cooxidation (4.6,20 pmol mg protein,1 min,1) and 4-hydroxylation (8.7,45 pmol mg protein,1 min,1) were quantitatively similar and exhibited similar individual variation (4 and 5 fold, respectively). From kinetic studies cooxidation was an efficient process in human hepatic microsomes (VmaxKm,1=0.25) compared with NADPH- and NADH-mediated 4-hydroxylation by CYP (VmaxKm,1=0.14 and 0.02, respectively). The capacity of lipid hydroperoxide metabolites of arachidonic acid to mediate ATRA oxidation was established directly, but downstream products (D, E, F and I-series prostaglandins) were inactive. cDNA-expressed CYPs supported ATRA oxidation by lipid hydroperoxides. Whereas CYPs 2C8, 2C9 and 3A4, but not CYPs 1A2 or 2E1, were effective catalysts of the NADPH-mediated reaction, cooxidation supported by 15(S)-hydroperoxyeicosatetraenoic acid was mediated by all five CYPs. The cooxidation reaction in human hepatic microsomes was inhibited by the CYP inhibitor miconazole. These findings indicate that ATRA oxidation is quantitatively significant in human liver. Lipid hydroperoxides generated by intracellular enzymes such as prostaglandin synthase and lipoxygenases are sources of activated oxygen for CYP-mediated deactivation of ATRA to polar products. British Journal of Pharmacology (2000) 131, 851,857; doi:10.1038/sj.bjp.0703579 [source] Efficacy of piperine, an alkaloidal constituent from Piper nigrum on erythrocyte antioxidant status in high fat diet and antithyroid drug induced hyperlipidemic ratsCELL BIOCHEMISTRY AND FUNCTION, Issue 6 2006Ramasamy Subramaniam Vijayakumar Abstract The main aim of this study was to investigate the effect of piperine on erythrocyte antioxidant status in high fat diet (HFD) and antithyroid drug induced hyperlipidemic rats. Male Wistar rats were divided into eight groups. The first four groups were fed a control diet and in addition were given respectively 1% carboxymethyl cellulose (CMC); 10,mg/kg body weight carbimazole (CM); 10,mg CM,+,40,mg/kg body weight piperine and 10,mg CM,+,2,mg/kg body weight atorvastatin (ATV). A similar pattern was followed for the next four groups except that they were all fed HFD instead of the control diet. Erythrocyte osmotic fragility, total cholesterol, phospholipids, lipid peroxidation products, enzymic and non-enzymic antioxidant status were studied in all experimental groups. Significantly increased osmotic fragility, total cholesterol/phospholipid ratio, thiobarbituric acid reactive substances and lipid hydroperoxides were observed in the plasma and erythrocytes of HFD fed and CM treated rats compared to the control. Superoxide dismutase, catalase, glutathione peroxidase, vitamin E and reduced glutathione in erythrocytes and vitamin C in the plasma were also significantly lowered in HFD fed, antithyroid drug treated rats compared to control animals. Concurrent piperine supplementation along with HFD and antithyroid drug administration normalized erythrocyte osmotic fragility, reduced lipid peroxidation, and improved the enzymic and non-enzymic antioxidant status compared to those rats that did not receive piperine. Thus, our results indicate that piperine supplementation markedly protects erythrocytes from oxidative stress by improving the antioxidant status in HFD fed antithyroid drug treated rats. Copyright © 2006 John Wiley & Sons, Ltd. [source] Lipid peroxide-induced redox imbalance differentially mediates CaCo-2 cell proliferation and growth arrestCELL PROLIFERATION, Issue 4 2002Yudai Gotoh Dietary oxidants like lipid hydroperoxides (LOOH) can perturb cellular glutathione/glutathione disulphide (GSH/GSSG) status and disrupt mucosal turnover. This study examines the effect of LOOH on GSH/GSSG balance and phase transitions in the human colon cancer CaCo-2 cell. LOOH at 1 or 5 µm were noncytotoxic, but disrupted cellular GSH/GSSG and stimulated proliferative activity at 6 h that paralleled increases in ornithine decarboxylase activity, thymidine incorporation, expression of cyclin D1/cyclin-dependent kinase 4, phosphorylation of retinoblastoma protein, and cell progression from G0/G1 to S. At 24 h, LOOH-induced sustained GSH/GSSG imbalance mediated growth arrest at G0/G1 that correlated with suppression of proliferative activity and enhanced oxidative DNA damage. LOOH-induced cell transitions were effectively blocked by N-acetylcysteine. Collectively, the study shows that subtoxic LOOH levels induce CaCo-2 GSH/GSSG imbalance that elicits time-dependent cell proliferation followed by growth arrest. These results provide insights into the mechanism of hydroperoxide-induced disruption of mucosal turnover with implications for understanding oxidant-mediated genesis of gut pathology. [source] The Role of One-Electron Reduction of Lipid Hydroperoxides in Causing DNA DamageCHEMISTRY - A EUROPEAN JOURNAL, Issue 40 2009Conor Crean Dr. Abstract The in vivo metabolism of plasma lipids generates lipid hydroperoxides that, upon one-electron reduction, give rise to a wide spectrum of genotoxic unsaturated aldehydes and epoxides. These metabolites react with cellular DNA to form a variety of pre-mutagenic DNA lesions. The mechanisms of action of the radical precursors of these genotoxic electrophiles are poorly understood. In this work we investigated the nature of DNA products formed by a one-electron reduction of (13S)-hydroperoxy-(9Z,11E)-octadecadienoic acid (13S -HPODE), a typical lipid molecule, and the reactions of the free radicals thus generated with neutral guanine radicals, G(,H).. A novel approach was devised to generate these intermediates in solution. The two-photon-induced ionization of 2-aminopurine (2AP) within the 2,-deoxyoligonucleotide 5,-d(CC[2AP]TCGCTACC) by intense nanosecond 308,nm excimer laser pulses was employed to simultaneously generate hydrated electrons and radical cations 2AP.+. The latter radicals either in cationic or neutral forms, rapidly oxidize the nearby G base to form G(,H).. In deoxygenated buffer solutions (pH,7.5), the hydrated electrons rapidly reduce 13S -HPODE and the highly unstable alkoxyl radicals formed undergo a prompt ,-scission to pentyl radicals that readily combine with G(,H).. Two novel guanine products in these oligonucleotides, 8-pentyl- and N2 -pentylguanine, were identified. It is shown that the DNA secondary structure significantly affects the ratio of 8-pentyl- and N2 -pentylguanine lesions that changes from 0.9:1 in single-stranded, to 1:0.2 in double-stranded oligonucleotides. The alkylation of guanine by alkyl radicals derived from lipid hydroperoxides might contribute to the genotoxic modification of cellular DNA under hypoxic conditions. Thus, further research is warranted on the detection of pentylguanine lesions and other alkylguanines in vivo. [source] |