Decomposition Of Lipid Hydroperoxides Research Articles

Studies with Myoglobin Variants Indicate that Released Hemin Is the Primary Promoter of Lipid Oxidation in Washed Fish Muscle

Variants of sperm whale myoglobin (Mb) were used to assess the mechanism of heme protein-mediated lipid oxidation in washed cod muscle. A myoglobin variant with high hemin affinity (V68T) was an exceptionally poor promoter of lipid oxidation, while a Mb variant with low hemin affinity (H97A) was a potent promoter of lipid oxidation. V68T releases hemin slowly due to the ability of threonine to hydrogen bond with coordinated water and the distal histidine within the heme crevice. H97A rapidly releases hemin because the relatively small alanine residue creates a channel for water to easily enter the heme crevice which weakens the covalent linkage of hemin to the proximal histidine. A variant sensitive to heme degradation (L29F/H64Q) was a weaker promoter of lipid oxidation compared to wild-type Mb. This suggests that degrading the heme ring and releasing iron decreased the ability of Mb to promote lipid oxidation. Free radicals resulting from hemin-mediated decomposition of lipid hydroperoxides have the capacity to propagate lipid oxidation and degrade hemin catalyst. This may explain why heme proteins behave as reactants rather than "catalysts" of lipid oxidation in washed cod. Collectively these studies strongly suggest that released hemin is the critical entity that drives heme protein-mediated lipid oxidation in washed fish muscle.

Endogenous Lipid Hydroperoxide-mediated DNA-adduct Formation in Min Mice

Despite intensive research over the last two decades, there are still no specific markers of endogenous lipid hydroperoxide-mediated DNA damage. We recently demonstrated that heptanone-etheno-2'-deoxyguanosine adducts are formed in the DNA of rat intestinal epithelial cells that stably express cyclooxygenase-2. Heptanone-etheno adducts can only arise from the reaction of lipid hydroperoxide-derived 4-oxo-2(E)-nonenal with DNA. This raised the possibility that similar adducts would be formed in vivo in settings where cyclooxygenase-2 expression is increased. Therefore, DNA-adduct formation was studied in C57BL/6JAPC(min) mice, a colorectal cancer mouse model in which cyclooxygenase-2 is up-regulated. 15(S)-Hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid is the major lipid hydroperoxide produced endogenously by cyclooxygenase-2. It undergoes homolytic decomposition to the DNA-reactive bifunctional electrophile 4-oxo-2(E)-nonenal, which forms heptanone-etheno adducts with DNA. A quantitative comparison was made of the heptanone-etheno-DNA adducts present in C57BL/6J and C57BL/6JAPC(min) mice. Using highly specific and sensitive methodology based on stable isotope dilution liquid chromatography/tandem mass spectrometry, we have detected the endogenous formation of heptanone-etheno adducts in mammalian tissue DNA for the first time. In addition, we found that there were statistically significant increased levels of the heptanone-etheno-2'-deoxyguanosine and heptanone-etheno-2'-deoxycytidine adducts in the C57BL/6JAPC(min) mice when compared with the control C57BL/6J mice.

Novel electrochemical approach to enhanced toxicity of 4-oxo-2-nonenal vs. 4-hydroxy-2-nonenal (role of imine): Oxidative stress and therapeutic modalities

Reactive oxygen species (ROS) and oxidative stress (OS) have received increasing attention in connection with illness, disease, and aging. The OS results in widespread attack of body constituents, with unsaturated lipids, leading to hydroperoxides, being a focus of research. Subsequent decomposition yields various functionalized aldehydes, including 4-hydroxy-2-nonenal (HNE). OS linked to HNE is associated with various illnesses. Recently, much attention has been devoted to 4-oxo-2-nonenal (ONE), also a product from lipid hydroperoxide decomposition. ROS and OS are increasingly implicated in the mode of action of drugs and toxins. The preponderance of bioactive substances or their metabolites incorporate electron transfer (ET) functionalities, among which are imines or iminiums. Also, in this category are the less well-known alpha-dicarbonyls. ET moieties undergo redox cycling accompanied by generation of ROS. Electrochemistry, a neglected area, can provide valuable insight. If the reduction potential is more positive than -0.5 V, then ET reactions are a possibility in vivo. Both HNE and ONE participate in Michael addition reactions with protein nucleophiles. The process occurs at a faster rate with ONE due mainly to the high reactivity toward His and Cys. The greater toxicity of ONE vs. HNE may partly reflect this difference. Also, ONE forms Schiff base (imine) at a faster rate than HNE, which also may contribute to the difference in toxicity. Electrochemistry of alpha-dicarbonyls and their imine derivatives can elucidate basic mechanisms. Methylglyoxal possesses a reduction potential of -0.18 V, amenable to ET in vivo. Since ONE is a vinylog of methylglyoxal, redox cycling should be even more facile. Another model is diacetyl whose reduction potential is also favorable. In contrast, crotonaldehyde, a model for the HNE vinylog, is characterized by a quite negative reduction potential, unsuitable for ET; acrolein is included. Imines of alpha-dicarbonyls serve as models for Schiff bases from ONE. The diimines in acid have reduction potentials of -0.45 to -0.49 V. Diacetyl monoxime, an oximino analog of the vinylogous ONE mono Schiff base, possesses a similar value. The ONE vinylogs should exhibit even better electrochemical characteristics. Thus, these neglected electrochemical properties can help rationalize the greater toxicity of ONE vs. HNE. Toxicity of the aldehydes may be countered by various approaches: formation of non-toxic imines, carboxylic acids, and Michael adducts. Genetic methods and AO therapy are treated.

Manipulation of systemic oxygen flux by acute exercise and normobaric hypoxia: implications for reactive oxygen species generation

Maximal exercise in normoxia results in oxidative stress due to an increase in free radical production. However, the effect of a single bout of moderate aerobic exercise performed in either relative or absolute normobaric hypoxia on free radical production and lipid peroxidation remains unknown. To examine this, we randomly matched {according to their normobaric normoxic VO2peak [peak VO2 (oxygen uptake)]} and assigned 30 male subjects to a normoxia (n = 10), a hypoxia relative (n = 10) or a hypoxia absolute (n = 10) group. Each group was required to exercise on a cycle ergometer at 55% of VO2peak for 2 h double-blinded to either a normoxic or hypoxic condition [FiO2 (inspired fraction of O2) = 0.21 and 0.16 respectively]. ESR (electron spin resonance) spectroscopy in conjunction with ex vivo spin trapping was utilized for the direct detection of free radical species. The main findings show that moderate intensity exercise increased plasma-volume-corrected free radical and lipid hydroperoxide concentration (pooled rest compared with exercise data, P < 0.05); however, there were no selective differences between groups (statexgroup interaction, P > 0.05). The delta change in free radical concentration was moderately correlated with systemic VO2 (r2 = 0.48, P < 0.05). The hyperfine coupling constants recorded from the ESR spectra [aN = 13.8 Gauss, and a(H)beta = 1.9 Gauss; where 1 Gauss = 10(-4) T (telsa)] are suggestive of oxygen-centred free radical species formed via the decomposition of lipid hydroperoxides. Peripheral leucocyte and neutrophil cells and total CK (creatine kinase) activity all increased following sustained exercise (pooled rest compared with exercise data, P < 0.05), but no selective differences were observed between groups (state x group interaction, P > 0.05). We conclude that a single bout of moderate aerobic exercise increases secondary free radical species. There is also evidence of exercise-induced muscle damage, possibly caused by the increase in free radical generation.

Oxidative stabilities of triacylglycerol and phospholipid fractions of cooked Japanese sardine meat during low temperature storage

Changes in triacylglycerols (TAG) and phospholipids (PL) compositions of cooked Japanese sardine meats as such or with prior addition of ethylene diaminetetracetic acid (EDTA) or a combination of nitrite and ascorbate were evaluated during chilled storage using gas chromatography and selected ion monitoring gas chromatography/mass spectrometry. The TAG molecular species compositions remained unchanged, while certain species of PL molecular species changed during storage at 2 °C for 14 days. The PL containing polyunsaturated fatty acids were highly susceptible to autoxidation. The PL fractions play an important role in oxidative rancidity and development of off-flavor in cooked sardine meat, while TAG fraction plays a minor role in the oxidative deterioration of the meat. Changes in peroxide and thiobarbituric acid values were also monitored. Added EDTA was not effective in controlling the decomposition of lipid hydroperoxide throughout the storage period. However, a combination of NaNO 2 and ascorbate not only suppressed the formation but also the decomposition of the primary oxidation products.

18O‐Labeled lipid hydroperoxides and HPLC coupled to mass spectrometry as valuable tools for studying the generation of singlet oxygen in biological system

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 ((1)O(2) in biological system. Using (18)O-labeled linoleic acid hydroperoxide (LA(18)O(18)OH) in the presence of Ce(4+) or Fe(2+), we observed the formation of (18)O-labeled (1)O(2) ((18)[(1)O(2)]) by chemical trapping of (1)O(2) with 9,10-diphenylanthracene (DPA) and detecting the corresponding (18)O-labeled DPA endoperoxide (DPA(18)O(18)O) by HPLC coupled to tandem mass spectrometry (HPLC-MS/MS). (18)O-Labeled alcohol and ketone were also detected providing further evidence for the generation of (1)O(2) by the Russell mechanism. Similarly the reaction of LA(18)O(18)OH with peroxynitrite also generated (18)[(1)O(2)].In conclusion, these results indicates that the use of (18)O-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.

Green tea protects against ethanol-induced lipid peroxidation in rat organs

Ethanol metabolism is accompanied by generation of free radicals, which stimulates lipid peroxidation. Natural antioxidants are particularly useful in such a situation. The current study was designed to investigate the efficacy of green tea, as a source of water-soluble antioxidants (catechins), on lipid peroxidation in liver, brain, and blood induced by chronic (4 weeks) ethanol intoxication in rats. Feeding of ethanol led to a significant increase in lipid peroxidation, as measured by increased concentrations of lipid hydroperoxides, 4-hydroxynonenal, and malondialdehyde. Feeding of ethanol also changed the glutathione-dependent lipid hydroperoxide decomposition system, resulting in a decrease in both reduced glutathione concentration and activity of glutathione peroxidase. Observed changes were statistically significant in all examined tissues. Enhancement in lipid peroxidation was associated with disruption of hepatocyte cell membranes, as observed through electron microscopic evaluation. Green tea protects phospholipids from enhanced peroxidation and prevents changes in biochemical parameters and morphologic changes observed after ethanol consumption. These results support the suggestion that green tea protects membranes from peroxidation of lipids associated with ethanol consumption.

A Novel Lipid Hydroperoxide-derived Cyclic Covalent Modification to Histone H4

Previous studies have established that 4-hydroxy-2-nonenal is a lipid hydroperoxide-derived aldehydic bifunctional electrophile that reacts with DNA and proteins. However, it has now been recognized that 4-oxo-2-nonenal is also a major product of lipid hydroperoxide decomposition. Furthermore, 4-oxo-2-nonenal is more reactive than 4-hydroxy-2-nonenal toward the DNA-bases 2'-deoxyguanosine, 2'-deoxyadenosine, and 2'-deoxycytidine and proteins. The formation of 4-oxo-2-nonenal can be induced through vitamin C-mediated or transition metal ion-mediated homolytic decomposition of polyunsaturated omega-3 lipid hydroperoxides such as 13(S)-hydroperoxyoctadecadienoic acid. We have discovered that synthetic 4-oxo-nonenal or 4-oxo-2-nonenal-generated from 13(S)-hydroperoxyoctadecadienoic acid recognizes the specific amino acid motifs of His75, Ala76, and Lys77 in bovine histone H4. Reaction of the histidine and lysine residues with 4-oxo-2-nonenal results in the formation of a novel cyclic structure within the protein. The cyclic structure incorporates the histidine imidazole ring and a newly formed pyrrole derived from the lysine. The cyclic imidazole-pyrrole derivative that is formed from the small Nalpha-acetyl-His-Ala-Lys peptide exists as a mixture of two atropisomers that inter-convert upon heating. Such lipid hydroperoxide-derived modifications could potentially modulate transcriptional activation in vivo. Furthermore, the ability to synthesize cyclic peptides using 4-oxo-2-nonenal will facilitate the preparation of novel structural analogs with potential biological activity.

Oxidative flavour deterioration of fish oil enriched milk

AbstractThe oxidative deterioration of milk emulsions supplemented with 1.5 wt‐% fish oil was investigated by sensory evaluation and by determining the peroxide value and volatile oxidation products after cold storage. Two types of milk emulsions were produced, one with a highly unsaturated tuna oil (38 wt‐% of n‐3 fatty acids) and one with cod liver oil (26 wt‐% of n‐3 fatty acids). The effect of added calcium disodium ethylenediaminetetraacetate (EDTA) on oxidation was also investigated. Emulsions based on cod liver oil with a slightly elevated peroxide value (1.5 meq/kg) oxidised significantly faster than the tuna oil emulsions, having a lower initial peroxide value (0.1 meq/kg). In the tuna oil emulsions the fishy off‐flavour could not be detected throughout the storage period. Addition of 5—50 ppm EDTA significantly reduced the development of volatile oxidation products in the cod liver oil emulsions, indicating that metal chelation with EDTA could inhibit the decomposition of lipid hydroperoxides in these emulsions. This study showed that an oxidatively stable milk emulsion containing highly polyunsaturated tuna fish oil could be prepared without significant fishy off‐flavour development upon storage, provided that the initial peroxide value was sufficiently low.

Mechanisms by which cysteine can inhibit or promote the oxidation of low density lipoprotein by copper

Oxidised low density lipoprotein (LDL) may play a role in atherogenesis. We have investigated some of the mechanisms by which the thiol cysteine and the disulphide cystine can influence the oxidation of LDL by copper ions. Cysteine or cystine (100 μM) inhibited the oxidation of native LDL by copper in a simple phosphate buffer. One of the mechanisms by which cysteine (or more likely its oxidation products in the presence of copper) and cystine inhibited LDL oxidation was by decreasing the binding of copper to LDL (97% inhibition). Cysteine, but not cystine, rapidly reduced Cu 2+ to Cu +. This may help to explain the antioxidant effect of cysteine as it may limit the amount of Cu 2+ that is available to convert α-tocopherol in LDL into the prooxidant α-tocopherol radical. Cysteine (but not cystine) had a prooxidant effect, however, toward partially oxidised LDL in the presence of a low copper concentration, which may have been due to the rapid breakdown of lipid hydroperoxides in partially oxidised LDL by Cu + generated by cysteine. To prove that cysteine can cause the rapid breakdown of lipid hydroperoxides in LDL, we enriched LDL with lipid hydroperoxides using an azo initiator in the absence of copper. Cysteine, but not cystine, increased the rate of lipid hydroperoxide decomposition to thiobarbituric acid-reactive substances (TBARS) in the presence of copper.

Singlet molecular oxygen generated from lipid hydroperoxides by the russell mechanism: studies using 18(O)-labeled linoleic acid hydroperoxide and monomol light emission measurements.

The decomposition of lipid hydroperoxides into peroxyl radicals is a potential source of singlet oxygen ((1)O(2)) in biological systems. We report herein on evidence of the generation of (1)O(2) from lipid hydroperoxides involving a cyclic mechanism from a linear tetraoxide intermediate proposed by Russell. Using (18)O-labeled linoleic acid hydroperoxide (LA(18)O(18)OH) in the presence of Ce(4+) or Fe(2+), we observed the formation of (18)O-labeled (1)O(2) ((18)[(1)O(2)]) by chemical trapping of (1)O(2) with 9,10-diphenylanthracene (DPA) and detected the corresponding (18)O-labeled DPA endoperoxide (DPA(18)O(18)O) by high-performance liquid chromatography coupled to tandem mass spectrometry. Spectroscopic evidence for the generation of (1)O(2) was obtained by measuring (i) the dimol light emission in the red spectral region (lambda > 570 nm); (ii) the monomol light emission in the near-infrared (IR) region (lambda = 1270 nm); and (iii) the quenching effect of sodium azide. Moreover, the presence of (1)O(2) was unequivocally demonstrated by the direct spectral characterization of the near-IR light emission. For the sake of comparison, (1)O(2) deriving from the H(2)O(2)/OCl(-) and H(2)O(2)/MoO(4)(2)(-) systems or from the thermolysis of the endoperoxide of 1,4-dimethylnaphthalene was also monitored. These chemical trapping and photoemission properties clearly demonstrate that the decomposition of LA(18)O(18)OH generates (18)[(1)O(2)], consistent with the Russell mechanism and pointing to the involvement of (1)O(2) in lipid hydroperoxide mediated cytotoxicity.

Exercise, free radicals, and lipid peroxidation in type 1 diabetes mellitus.

Indirect biochemical techniques have solely been used to ascertain whether type 1 diabetes mellitus patients are more susceptible to resting and exercise-induced oxidative stress. To date there is no direct evidence to support the contention that type 1 diabetic patients have increased levels of free radical species. Thus, the aim of this study was to use electron spin resonance (ESR) spectroscopy in conjunction with alpha-phenyl-tert-butylnitrone (PBN) spin trapping to measure pre- and postexercise free radical concentration in the venous blood of young male patients with type 1 diabetes mellitus (HbA(1c) = 8.2 +/- 1%, n = 12) and healthy matched controls (HbA(1c) = 5.5 +/- 0.2%, n = 13). Supporting measures of lipid peroxidation (malondialdehyde and lipid hydroperoxides), ambient blood glucose and selected antioxidants were also measured. The diabetic patients presented with a comparatively greater concentration of free radicals as measured by ESR and lipid hydroperoxides (LH) compared to the healthy group (p <.05, pooled rest and exercise data), although there was no difference in malondialdehyde (MDA) concentration. alpha-Tocopherol was comparatively lower in the healthy group (p <.05, pooled rest and exercise data vs. diabetic group) due to a selective decrease during physical exercise (p <.05 vs. rest). The hyperfine coupling constants recorded from the ESR spectra (a(Nitrogen) = 1.37 mT and abeta(Hydrogen) = 0.17 mT) are suggestive of either oxygen or carbon-centered species and are consistent with literature values. We suggest that the greater concentration of oxidants seen in the diabetic group may be due to increased glucose autoxidation as a function of this pathology and/or a lower exercise-induced oxidation rate of the major lipid soluble antioxidant alpha-tocopherol. We suggest that the ESR-detected radicals are secondary species derived from decomposition of LH because these are the major initial reaction products of free radical attack on cell membranes.

4,5-Epoxy-2(E)-decenal-induced formation of 1,N(6)-etheno-2'-deoxyadenosine and 1,N(2)-etheno-2'-deoxyguanosine adducts.

trans-4,5-Epoxy-2(E)-decenal reacted with 2'-deoxyadenosine to give 1,N(6)-etheno-2'-deoxyadenosine as well as other 2'-deoxyadenosine adducts. It also reacted with 2'-deoxyguanosine to give 1,N(2)-etheno-2'-deoxyguanosine and other 2'-deoxyguanosine adducts. Synthetic trans-4,5-epoxy-2(E)-decenal was quite stable under the reaction conditions that were used. It was not contaminated with 2,3-epoxyoctanal, a potential precursor to the formation of unsubstituted etheno adducts. Furthermore, using a sensitive LC/MS assay, it was possible to show that no 2,3-epoxyoctanal was formed during prolonged incubations of trans-4,5-epoxy-2(E)-decenal. Therefore, trans-4,5-epoxy-2(E)-decenal, a primary product of lipid peroxidation, is a precursor to the formation of 1,N(6)-etheno-2'-deoxyadenosine and 1,N(2)-etheno-2'-deoxyguanosine. There is no need for an additional oxidation step such as would be required if trans,trans-2,4-decadienal or 4-hydroxy-2-nonenal were the lipid hydroperoxide decomposition products that initiated the formation of unsubstituted etheno adducts. These findings provide an important link between a primary product of lipid peroxidation and a mutagenic DNA lesion that has been detected in human tissues.

ChemInform Abstract: Vitamin C Induced Decomposition of Lipid Hydroperoxides: Direct Evidence of Genotoxin‐DNA Binding Detected by QCRS.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Lipid hydroperoxide-mediated DNA damage.

Lipid hydroperoxides are formed in vivo through free radical pathways from the action of reactive oxygen species on polyunsaturated fatty acids. They are also formed as specific products of lipoxygenases and cyclooxygenases. Homolytic decomposition of lipid hydroperoxides to the alpha,beta-unsaturated aldehyde genotoxins, 4-oxo-2-nonenal, 4,5-epoxy-2(E)-decenal, and 4-hydroxy-2-nonenal occurs through two quite distinct pathways. One pathway involves a complex rearrangement of the alkoxy radical derived from the lipid hydroperoxide and the other pathway involves the intermediate formation of another potential genotoxin, 4-hydroperoxy-2-nonenal. 4,5-Epoxy-2(E)-decenal forms the unsubstituted etheno-2-deoxyadenosine adduct with DNA, a mutagenic lesion which has been observed in human tissue DNA samples. Several new ethano- and etheno-DNA-adducts have been identified from the reaction of 4-oxo-2-nonenal with DNA. 4-Hydroxy-2-nonenal forms propano adducts with 2'-deoxyguanosine. It can also up-regulate cyclooxygenase-2 expression. As cyclooxygenase-2 converts linoleic acid into lipid hydroperoxides, this provides a potential mechanism for increased production of genotoxic bifunctional electrophiles. Malondialdehyde (beta-hydroxy-acrolein), another genotoxic bifunctional electrophile, is formed during homolytic decomposition of lipid hydroperoxides that contain more than two double bonds. Other sources of malondialdehyde include, hydroxyl radical-mediated decomposition of the 2'-deoxyribose DNA backbone and formation as a side-product during the biosynthesis of thromboxane A(2). Malondialdehyde reacts with DNA to form primarily a propano adduct with 2'-deoxyguanosine (M(1)G-dR). Significant advances in the characterization and analysis of lipid hydroperoxide-derived endogenous DNA-adducts have been made over the last decade so that dosimetry studies of human populations are now possible. Such studies will help elucidate the role of lipid hydroperoxide-derived endogenous DNA as mediators of cancer,

Vitamin caution

Vitamin C is not the panacea it was once believed to be. In fact, it's been found to induce the formation of genotoxins. Vitamin C has been proposed as a dietary supplement to prevent cancer because of its antioxidant properties. However, it has proved ineffective in clinical trials. Now, Ian Blair's group at the Center for Cancer Pharmacology, University of Pennsylvania (PA, USA) provides an explanation. Their results, published in June in the journal Science, show that vitamin C can enhance the in vitro decomposition of lipid hydroperoxides to DNA-damaging agents called bifunctional electrophiles. They used vitamin C concentrations that correspond to a daily dose of 200 milligrams. Blair says that ‘it's possible that vitamin C isn't working in cancer prevention studies because it's causing as much damage as it's preventing.’ JW

Oxidation in fish oil enriched mayonnaise: ascorbic acid and low pH increase oxidative deterioration.

The effect of ascorbic acid (0-4000 ppm) and pH (3.8-6.2) on oxidation and levels of iron and copper in various fractions of mayonnaise enriched with 16% fish oil was investigated. Ascorbic acid induced release of iron from the assumed oil-water interface into the aqueous phase at all pH levels, but this effect of ascorbic acid was strongest at low pH (pH 3.8-4.2). Ascorbic acid generally promoted formation of volatile oxidation compounds and reduced the peroxide value in mayonnaises. Peroxide values and total volatiles generally increased with decreasing pH values, suggesting that low pH promoted oxidation. It is proposed that iron bridges between the egg yolk proteins low-density lipoproteins, lipovitellin, and phosvitin at the oil-water interface are broken at low pH values, whereby iron ions become accessible as oxidation initiators. In the presence of ascorbic acid, oxidation is further enhanced due to the reduction of Fe(3+) to Fe(2+) that rapidly catalyzes lipid oxidation via lipid hydroperoxide decomposition at the oil-water interface in mayonnaise.

Vitamin C-induced decomposition of lipid hydroperoxides to endogenous genotoxins.

Epidemiological data suggest that dietary antioxidants play a protective role against cancer. This has led to the proposal that dietary supplementation with antioxidants such as vitamin C (vit C) may be useful in disease prevention. However, vit C has proved to be ineffective in cancer chemoprevention studies. In addition, concerns have been raised over potentially deleterious transition metal ion-mediated pro-oxidant effects. We have now determined that vit C induces lipid hydroperoxide decomposition to the DNA-reactive bifunctional electrophiles 4-oxo-2-nonenal, 4,5-epoxy-2(E)-decenal, and 4-hydroxy-2-nonenal. The compound 4,5-Epoxy-2(E)-decenal is a precursor of etheno-2'-deoxyadenosine, a highly mutagenic lesion found in human DNA. Vitamin C-mediated formation of genotoxins from lipid hydroperoxides in the absence of transition metal ions could help explain its lack of efficacy as a cancer chemoprevention agent.

Lipid Oxidation in Fish Oil Enriched Mayonnaise: Calcium Disodium Ethylenediaminetetraacetate, but Not Gallic Acid, Strongly Inhibited Oxidative Deterioration

The antioxidative effects of gallic acid, EDTA, and extra emulsifier Panodan DATEM TR in mayonnaise enriched with 16% fish oil were investigated. EDTA reduced the formation of free radicals, lipid hydroperoxides, volatiles, and fishy and rancid off-flavors. The antioxidative effect of EDTA was attributed to its ability to chelate free metal ions and iron from egg yolk located at the oil-water interface. Gallic acid reduced the levels of both free radicals and lipid hydroperoxides but promoted slightly the oxidative flavor deterioration in mayonnaise and influenced the profile of volatiles. Gallic acid may therefore promote the decomposition of lipid hydroperoxides to volatile oxidation products. Addition of extra emulsifier reduced the lipid hydroperoxide levels but did not influence the level of free radicals or the oxidative flavor deterioration in mayonnaisse; however, it appeared to alter the profile of volatiles. The effect of the emulsifier on the physical structure and rheological properties depended on the presence of antioxidants.

Vitamin C induced decomposition of lipid hydroperoxides: direct evidence of genotoxin-DNA binding detected by QCRS.

We report direct evidence for human DNA-binding to precursors of mutagenic lesion-inducing compounds, produced form the vitamin C induced decomposition of lipid hydroperoxides, using a quartz crystal resonant sensor assay.