Lipid Peroxyl Radicals Research Articles

Antioxidant Activity of Bilirubin in Micellar and Liposomal Systems Is pH-Dependent.

Bilirubin (BR), a product of heme catabolism, plays a critical role in biological systems. Although increased levels of BR result in hyperbilirubinemia or jaundice, there is increasing evidence that lower concentrations substantially decrease the risk of oxidative stress-mediated diseases due to antioxidant functions of BR. We studied the radical-trapping ability of BR in two model systems, micellar and liposomal, at a broad pH range. At pH < 6.0, BR behaves as a retardant; however, at pH ≥ 6.0, BR becomes strong radical trapping antioxidant, with rate constants for reaction with lipidperoxyl radicals (kinh) within the range from 1.2 × 104 M-1 s-1 to 3.5 × 104 M-1 s-1, and in liposomal system, the activity of BR is comparable to α-tocopherol. This transition is likely facilitated by the ionization of carboxyl groups, leading to a conformational shift in BR and improved solubility/localization at the water/lipid interface. This is the first experimental evidence of the role of pH on the antioxidant activity of bilirubin, and the observed pH-dependent radical-trapping ability of BR holds practical significance, particularly in jaundice treatment where light therapy targets the skin's weakly acidic surface. Minor adjustments toward neutral or alkaline pH can enhance radical-trapping action of BR, thereby mitigating oxidative stress induced with blue or violet light exposure.

Formation of free acetaldehydes derived from lipid peroxidation in U937 monocyte-like cells

Acetaldehyde can be found in human cells as a byproduct of various metabolic pathways, including oxidative processes such as lipid peroxidation. This secondary product of lipid peroxidation plays a role in various pathological processes, leading to various types of civilization diseases. In this study, the formation of free acetaldehyde induced by oxygen-centred radicals was studied in monocyte-like cell line U937. Exposure of U937 cells to peroxyl/alkoxyl radicals induced by azocompound resulted in the formation of free acetaldehyde. Acetaldehyde is formed by the cleavage of fatty acids, which represents the breakdown of fatty acids into smaller fragments initiated by the cyclization of lipid peroxyl radical and β-scission of lipid alkoxyl radical. The cleavage of fatty acids alters the integrity of the plasma and nuclear membrane, leading to the loss of cell viability. Understanding the pathological processes of acetaldehyde formation is an active area of research with potential implications for preventing and treating various diseases associated with oxidative stress.

Potential role of tocopherol in protecting crop plants against abiotic stresses.

The changing global climate have given rise to abiotic stresses that adversely affect the metabolic activities of plants, limit their growth, and agricultural output posing a serious threat to food production. The abiotic stresses commonly lead to production of reactive oxygen species (ROS) that results in cellular oxidation. Over the course of evolution, plants have devised efficient enzymatic and non-enzymatic anti-oxidative strategies to counteract harmful effects of ROS. Among the emerging non-enzymatic anti-oxidative technologies, the chloroplast lipophilic antioxidant vitamin A (Tocopherol) shows great promise. Working in coordination with the other cellular antioxidant machinery, it scavenges ROS, prevents lipid peroxidation, regulates stable cellular redox conditions, simulates signal cascades, improves membrane stability, confers photoprotection and enhances resistance against abiotic stresses. The amount of tocopherol production varies based on the severity of stress and its proposed mechanism of action involves arresting lipid peroxidation while quenching singlet oxygen species and lipid peroxyl radicals. Additionally, studies have demonstrated its coordination with other cellular antioxidants and phytohormones. Despite its significance, the precise mechanism of tocopherol action and signaling coordination are not yet fully understood. To bridge this knowledge gap, the present review aims to explore and understand the biosynthesis and antioxidant functions of Vitamin E, along with its signal transduction and stress regulation capacities and responses. Furthermore, the review delves into the light harvesting and photoprotection capabilities of tocopherol. By providing insights into these domains, this review offers new opportunities and avenues for using tocopherol in the management of abiotic stresses in agriculture.

In vitro radical-scavenging mechanism of melatonin and its in vivo protective effect against radiation-induced lipid peroxidation

Melatonin (N-acetyl-5-methoxytryptamine, MLT), an evolutionarily conserved indoleamine, is known to act as an antioxidant. However, the evidence indicating the role of MLT as a powerful chain-breaking antioxidant by scavenging peroxyl radical remains controversial. The radical-scavenging rate of MLT determined in this study in methanol using galvinoxyl radical (GO•) was much lower than that of an α-tocopherol model compound. The acceleration of the GO•-scavenging reaction by MLT was observed in the presence of magnesium ion (Mg2+), a bio-related redox-inactive metal ion, suggesting that this reaction may proceed via a rate-determining electron transfer followed by proton transfer. The coordination of Mg2+ to the carbonyl oxygen in the one-electron reduced species of GO• (GO–) may stabilize the product, resulting in the acceleration of the electron-transfer process. We also demonstrated that prophylactically administrated MLT efficiently inhibited the lipid peroxide-derived protein modification, which can be detected by a sensitive marker, Nε-(hexanoyl)lysine adduct, in the plasma of X-irradiated mice. The relatively weak GO•-scavenging activity of MLT suggests that the ameliorative effect of MLT against in vivo lipid peroxidation does not result from the direct scavenging of lipid peroxyl radicals by MLT. Therefore, the observed superior protective efficiency of MLT against in vivo lipid peroxidation may partly support the earlier studies, which reported the synergistic antioxidative effect of the metabolites of MLT.

The antioxidant glutathione.

Reduced glutathione (GSH) is an essential non-enzymatic antioxidant in mammalian cells. GSH can act directly as an antioxidant to protect cells against free radicals and pro-oxidants, and as a cofactor for antioxidant and detoxification enzymes such as glutathione peroxidases, glutathione S-transferases, and glyoxalases. Glutathione peroxidases detoxify peroxides by a reaction that is coupled to GSH oxidation to glutathione disulfide (GSSG). GSSG is converted back to GSH by glutathione reductase and cofactor NADPH. GSH can regenerate vitamin E following detoxification reactions of vitamin E with lipid peroxyl radicals (LOO). GSH is a cofactor for GST during detoxification of electrophilic substances and xenobiotics. Dicarbonyl stress induced by methylglyoxal and glyoxal is alleviated by glyoxalase enzymes and GSH. GSH regulates redox signaling through reversible oxidation of critical protein cysteine residues by S-glutathionylation. GSH is involved in other cellular processes such as protein folding, protecting protein thiols from oxidation and crosslinking, degradation of proteins with disulfide bonds, cell cycle regulation and proliferation, ascorbate metabolism, apoptosis and ferroptosis.

Damage of amino acids by aliphatic peroxyl radicals: a kinetic and computational study.

Absolute second-order rate coefficients for the reaction of the N- and C-protected amino acids tyrosine (Tyr), tryptophan (Trp), methionine (Met) and proline (Pro) with triethylamine-derived aliphatic peroxyl radical TEAOO˙, which was used as a model for lipid peroxyl radicals, were determined using laser flash photolysis. For Ac-Tyr-OMe a rate coefficient of 1.4 × 104 M-1 s-1 was obtained, whereas the reactions with Ac-Trp-OMe and Ac-Met-OMe were slower by a factor of 4 and 6, respectively. For the reaction with Ac-Pro-OMe only an upper value of 103 M-1 s-1 could be determined, suggesting that Pro residues are not effective traps for lipid peroxyl radicals. Density functional theory (DFT) calculations revealed that the reactions proceed via radical hydrogen atom transfer (HAT) from the Cα position, indicating that the rate is determined by the exothermicity of the reaction. In the case of Ac-Tyr-OMe, HAT from the phenolic OH group is the kinetically preferred pathway, which shuts down when hydrogen bonding with an amine occurs. In an alkaline environment, where the phenolic OH group is deprotonated, the reaction is predicted to occur preferably at Cβ, likely through a proton-coupled electron transfer (PCET) mechanism.

Anti-Oxidant and Anti-Inflammatory Effects of Astaxanthin on Gastrointestinal Diseases.

A moderate amount of reactive oxygen species (ROS) is produced under normal conditions, where they play an important role in cell signaling and are involved in many aspects of the immune response to pathogens. On the other hand, the excessive production of ROS destructs macromolecules, cell membranes, and DNA, and activates pro-inflammatory signaling pathways, which may lead to various pathologic conditions. Gastrointestinal (GI) mucosa is constantly exposed to ROS due to the presence of bacteria and other infectious pathogens in food, as well as alcohol consumption, smoking, and the use of non-steroidal anti-inflammatory drugs (NSAID). Prolonged excessive oxidative stress and inflammation are two major risk factors for GI disorders such as ulcers and cancers. Bioactive food compounds with potent anti-oxidant and anti-inflammatory activity have been tested in experimental GI disease models to evaluate their therapeutic potential. Astaxanthin (AST) is a fat-soluble xanthophyll carotenoid that is naturally present in algae, yeast, salmon, shrimp, and krill. It has been shown that AST exhibits protective effects against GI diseases via multiple mechanisms. Residing at the surface and inside of cell membranes, AST directly neutralizes ROS and lipid peroxyl radicals, enhances the activity of anti-oxidant enzymes, and suppresses pro-inflammatory transcription factors and cytokines. In addition, AST has been shown to inhibit cancer cell growth and metastasis via modulating cell proliferation-related pathways, apoptosis, and autophagy. Considering the potential benefits of AST in GI diseases, this review paper aims to summarize recent advances in AST research, focusing on its anti-oxidant and anti-inflammatory effects against gastric and intestinal ulcers and cancers.

Tanshinone functions as a coenzyme that confers gain of function of NQO1 to suppress ferroptosis.

Ferroptosis is triggered by the breakdown of cellular iron-dependent redox homeostasis and the abnormal accumulation of lipid ROS. Cells have evolved defense mechanisms to prevent lipid ROS accumulation and ferroptosis. Using a library of more than 4,000 bioactive compounds, we show that tanshinone from Salvia miltiorrhiza (Danshen) has very potent inhibitory activity against ferroptosis. Mechanistically, we found that tanshinone functions as a coenzyme for NAD(P)H:quinone oxidoreductase 1 (NQO1), which detoxifies lipid peroxyl radicals and inhibits ferroptosis both in vitro and in vivo. Although NQO1 is recognized as an oxidative stress response gene, it does not appear to have a direct role in ferroptosis inhibition in the absence of tanshinone. Here, we demonstrate a gain of function of NQO1 induced by tanshinone, which is a novel mechanism for ferroptosis inhibition. Using mouse models of acute liver injury and ischemia/reperfusion heart injury, we observed that tanshinone displays protective effects in both the liver and the heart in a manner dependent on NQO1. Our results link the clinical use of tanshinone to its activity in ferroptosis inhibition.

Role of Tocochromanols in Tolerance of Cereals to Biotic Stresses: Specific Focus on Pathogenic and Toxigenic Fungal Species.

Fungal pathogens capable of producing mycotoxins are one of the main threats to the cultivation of cereals and the safety of the harvested kernels. Improving the resistance of crops to fungal disease and accumulation of mycotoxins is therefore a crucial issue. Achieving this goal requires a deep understanding of plant defense mechanisms, most of them involving specialized metabolites. However, while numerous studies have addressed the contribution of phenylpropanoids and carotenoids to plant chemical defense, very few have dealt with tocochromanols. Tocochromanols, which encompass tocopherols and tocotrienols and constitute the vitamin E family, are widely distributed in cereal kernels; their biosynthetic pathway has been extensively studied with the aim to enrich plant oils and combat vitamin E deficiency in humans. Here we provide strong assumptions arguing in favor of an involvement of tocochromanols in plant–fungal pathogen interactions. These assumptions are based on both direct effects resulting from their capacity to scavenge reactive oxygen species, including lipid peroxyl radicals, on their potential to inhibit fungal growth and mycotoxin yield, and on more indirect effects mainly based on their role in plant protection against abiotic stresses.

Intrinsic and Extrinsic Limitations to the Design and Optimization of Inhibitors of Lipid Peroxidation and Associated Cell Death.

The archetype inhibitors of ferroptosis, ferrostatin-1 and liproxstatin-1, were identified via high-throughput screening of compound libraries for cytoprotective activity. These compounds have been shown to inhibit ferroptosis by suppressing propagation of lipid peroxidation, the radical chain reaction that drives cell death. Herein, we present the first rational design and optimization of ferroptosis inhibitors targeting this mechanism of action. Engaging the most potent radical-trapping antioxidant (RTA) scaffold known (phenoxazine, PNX), and its less reactive chalcogen cousin (phenothiazine, PTZ), we explored structure-reactivity-potency relationships to elucidate the intrinsic and extrinsic limitations of this approach. The results delineate the roles of inherent RTA activity, H-bonding interactions with phospholipid headgroups, and lipid solubility in determining activity/potency. We show that modifications which increase inherent RTA activity beyond that of the parent compounds do not substantially improve RTA kinetics in phospholipids or potency in cells, while modifications that decrease intrinsic RTA activity lead to corresponding erosions to both. The apparent "plateau" of RTA activity in phospholipid bilayers (kinh ∼ 2 × 105 M-1 s-1) and cell potency (EC50 ∼ 4 nM) may be the result of diffusion-controlled reactivity between the RTA and lipid-peroxyl radicals and/or the potential limitations on RTA turnover/regeneration by endogenous reductants. The metabolic stability of selected derivatives was assessed to identify a candidate for in vivo experimentation as a proof-of-concept. This PNX-derivative demonstrated stability in mouse liver microsomes comparable to liproxstatin-1 and was successfully used to suppress acute renal failure in mice brought on by tissue-specific inactivation of the ferroptosis regulator GPX4.

Studies on in vitro Radical Scavenging Potentials of Methanol Leaf Extract of Ficus sur and its Fractions

Background: In many rural areas of Nigeria, Ficus sur is traditionally used in the management of many diseases some of whose pathogenesis implicate free radicals. Objectives: To determine the phenolic contents and the in vitro radical scavenging activities of methanol extracts of Ficus sur (MEFS) and its hydromethanol (HMFS), ethyl acetate (EAFS) and hexane (HFFS) fractions. Materials and Methods: The leaves of Ficus sur were air dried, extracted with absolute methanol, and then partitioned sequentially with hexane and ethyl acetate. The phenolic contents of the parent extract and the fractions were determined. The scavenging activities of the extracts towards 1,1diphenyl-2-picryl hydrazyl (DPPH), hydroxyl, propagating lipid peroxyl and nitric oxide radicals were examined quantitatively. Results: Total phenol, flavonols and flavonoids were high in MEFS, moderate in EAFS and low in HFFS. The extracts scavenged DPPH radical (IC50 = 42.35± 3.55- 169.43 ± 16.43 , hydroxyl radical (IC50 = 55.58 ±8.16- 318.33± 14), peroxyl radical (IC50 = 60.33± 13.8- 219± 36.44 μg/ml) and nitric oxide radical (IC50 = 41.94 ±6.65- 210.5 ± 11.3 μg/ml) in a dose-dependent manner. The flavonoid contents of the extracts inversely correlated with the IC50 values of free radical scavenging activities. Overall, the radical scavenging abilities of MEFS and its fraction follow the order: MEFS&gt; HMFS&gt; EAFS&gt; HFFS. Conclusion: Hence, it may be concluded that extracts that have higher phenolic contents are superior to those with lower phenolic contents in radical scavenging activities, which cement the fact that, indeed, phenolics are largely responsible for the invitro antioxidant activities of the plant extracts.

An evolutionary conserved detoxification system for membrane lipid-derived peroxyl radicals in Gram-negative bacteria.

How double-membraned Gram-negative bacteria overcome lipid peroxidation is virtually unknown. Bactericidal antibiotics and superoxide ion stress stimulate the transcription of the Burkholderia cenocepacia bcnA gene that encodes a secreted lipocalin. bcnA gene orthologs are conserved in bacteria and generally linked to a conserved upstream gene encoding a cytochrome b561 membrane protein (herein named lcoA, lipocalin-associated cytochrome oxidase gene). Mutants in bcnA, lcoA, and in a gene encoding a conserved cytoplasmic aldehyde reductase (peroxidative stress-associated aldehyde reductase gene, psrA) display enhanced membrane lipid peroxidation. Compared to wild type, the levels of the peroxidation biomarker malondialdehyde (MDA) increase in the mutants upon exposure to sublethal concentrations of the bactericidal antibiotics polymyxin B and norfloxacin. Microscopy with lipid peroxidation-sensitive fluorescent probes shows that lipid peroxyl radicals accumulate at the bacterial cell poles and septum and peroxidation is associated with a redistribution of anionic phospholipids and reduced antimicrobial resistance in the mutants. We conclude that BcnA, LcoA, and PsrA are components of an evolutionary conserved, hitherto unrecognized peroxidation detoxification system that protects the bacterial cell envelope from lipid peroxyl radicals.

Structure–antioxidant activity (oxygen radical absorbance capacity) relationships of phenolic compounds

Antioxidant capacity is the extent to which a compound can eliminate reactive oxygen species, and in vitro methods for its chemical evaluation have been proposed. Among these methods, the oxygen radical absorbance capacity (ORAC) assay comes close to the oxidation reaction in the living body because it generates radical species that mimic the lipid peroxyl radical involved in the peroxidation reaction of biological components and react in a phosphate buffer. In this study, PM7, a semi-empirical molecular orbital method, was used to calculate the thermodynamic properties (bond dissociation enthalpy, ionisation potential and proton affinity) associated with ORAC. We also applied the clusterwise linear regression analysis as a statistical method for grouping the antioxidants by structure. By analysing the data for antioxidants, the trend in the hydrophilic ORAC values was determined using the calculated structures and bond dissociation enthalpies of the groups classified according to the presence or absence of oxygen functional groups in the ortho position of phenol. Further studies of indicators other than bond dissociation enthalpy are needed to predict the ORAC of other antioxidants such as flavonoids and indoles.

Unexpected Role of pH and Microenvironment on the Antioxidant and Synergistic Activity of Resveratrol in Model Micellar and Liposomal Systems.

Experimental and theoretical studies indicate that resveratrol (RSV, dietary polyphenol that effectively reduces cellular oxidative stress) is a good scavenger of hydroxyl, alkoxyl, and peroxyl radicals in homogeneous systems. However, the role of RSV as a chain-breaking antioxidant is still questioned. Here, we describe pH dependent effectiveness of RSV as an inhibitor of peroxidation of methyl linoleate in Triton X-100 micelles and in 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes, with the best effectiveness at pH 6 (stoichiometric factors, n, are 4.9 and 5.6, and the rate constants for reaction with peroxyl radicals, kinh, are 1200 and 3300 M–1 s–1 in micellar and liposomal systems, respectively). We propose the mechanism in which RSV-derived radicals are coupled to dimers with recovered ability to trap lipidperoxyl radicals. The formation of such dimers is facilitated due to increased local concentration of RSV at the lipid–water interface. Good synergy of RSV with α-tocopherol analogue in micelles and liposomes is in contrast to the previously reported lack of synergy in non-polar solvents; however, the increased persistency of tocopheroxyl radicals in dispersed lipid/water systems and proximal localization of both antioxidants greatly facilitate the possible recovery of α-TOH by RSV.

Lipid oxidation that is, and is not, inhibited by vitamin E: Consideration about physiological functions of vitamin E

Lipids are oxidized in vivo by multiple oxidizing species with different properties, some by regulated manner to produce physiological mediators, while others by random mechanisms to give detrimental products. Vitamin E plays an important role as a physiologically essential antioxidant to inhibit unregulated lipid peroxidation by scavenging lipid peroxyl radicals to break chain propagation independent of the type of free radicals which induce chain initiation. Kinetic data suggest that vitamin E does not act as an efficient scavenger of nitrogen dioxide radical, carbonate anion radical, and hypochlorite. The analysis of regio- and stereo-isomer distribution of the lipid oxidation products shows that, apart from lipid oxidation by CYP enzymes, the free radical-mediated lipid peroxidation is the major pathway of lipid oxidation taking place in humans. Compared with healthy subjects, the levels of racemic and trans,trans-hydro (pero)xyoctadecadienoates, specific biomarker of free radical lipid oxidation, are elevated in the plasma of patients including atherosclerosis and non-alcoholic fatty liver diseases. α-Tocopherol acts as a major antioxidant, while γ-tocopherol scavenges nitrogen dioxide radical, which induces lipid peroxidation, nitration of aromatic compounds and unsaturated fatty acids, and isomerization of cis-fatty acids to trans-fatty acids. It is essential to appreciate that the antioxidant effects of vitamin E depend on the nature of both oxidants and substrates being oxidized. Vitamin E, together with other antioxidants such as vitamin C, contributes to the inhibition of detrimental oxidation of biological molecules and thereby to the maintenance of human health and prevention of diseases.

Overexpression of 4-hydroxyphenylpyruvate dioxygenase (IbHPPD) increases abiotic stress tolerance in transgenic sweetpotato plants

Tocopherols are lipid-soluble compounds regarded as vitamin E compounds and they function as antioxidants in scavenging lipid peroxyl radicals and quenching reactive oxygen species (ROS). In our previous studies, we isolated five tocopherol biosynthesis genes from sweetpotato (Ipomoea batatas [L.] Lam) plants including 4-hydroxyphenylpyruvate dioxygenase (IbHPPD). HPPD is the first regulatory enzyme in vitamin E biosynthesis and serves to catalyze in the first steps α-tocopherol and plastoquinone biosynthesis by converting 4-hydroxyphenylpyruvate (HPP) to homogentisic acid (HGA). In this study, we generated transgenic sweetpotato plants overexpressing IbHPPD under the control of cauliflower mosaic virus (CaMV) 35S promoter (referred to as HP plants) via Agrobacterium-mediated transformation to understand the function of IbHPPD in sweetpotato. Three transgenic lines (HP3, HP14 and HP15) with high transcript levels of IbHPPD were selected for further characterization. Compared with non-transgenic (NT) plants, HP plants exhibited enhanced tolerance to multiple environmental stresses, including salt, drought, and oxidative stresses. In addition, HP plants showed increased tolerance to the herbicide sulcotrione, which is involved in the inhibition of the HPPD. Interestingly, after stress treatments, HP plants also showed higher abscisic acid (ABA) contents than NT plants. Under dehydrated condition, HP plants displayed an elevated α-tocopherol content to 19–27% in leaves compared with NT plants. These results indicate that increased abiotic stress tolerance in HP plants is related to inducing enhancement of α-tocopherol and ABA contents.

Generation of singlet oxygen via iron-dependent lipid peroxidation and its role in Ferroptosis

Ferroptosis is a cell death pathway mediated by iron-dependent accumulation of lipid peroxide. However, the specific downstream molecular events of iron-dependent lipid peroxidation are yet to be elucidated. In this study, based on various spectral analyses, we have found evidence that singlet oxygen is produced through the Russell mechanism during the self-reaction of lipid peroxyl radicals generated via iron-dependent lipid peroxidation regardless of the presence of cholesterol. Significantly reduced generation of singlet oxygen was observed in the absence of iron. The generated singlet oxygen accelerated the oxidative damage of lipid membranes by propagating lipid peroxidation and facilitated ferroptotic cancer cell death initiated by erastin. In this work, singlet oxygen has been revealed to be a new reactive species that participates in ferroptosis, thus improving the understanding on iron-dependent lipid peroxidation and the mechanism of ferroptosis.

Urinary oxidized, but not enzymatic vitamin E metabolites are inversely associated with measures of glucose homeostasis in middle-aged healthy individuals

Damage induced by lipid peroxidation has been associated with impaired glucose homeostasis. Vitamin E (α-tocopherol, α-TOH) competitively reacts with lipid peroxyl radicals to mitigate oxidative damage, and forms oxidized vitamin E metabolites. Accordingly, we aimed to investigate the associations between α-TOH metabolites (oxidized and enzymatic) in both circulation and urine and measures of glucose homeostasis in the general middle-aged population. This cross-sectional study was embedded in the population-based Netherlands Epidemiology of Obesity (NEO) Study. α-TOH metabolites in blood (α-TOH and α-CEHC-SO3) and urine [sulfate (SO3) and glucuronide (GLU) of both α-TLHQ (oxidized) and α-CEHC (enzymatic)] were quantified by liquid chromatography coupled with tandem mass spectrometry (LC/MS-MS). Measures of glucose homeostasis (HOMA-B, HOMA-IR, Insulinogenic index and Matsuda index) were obtained from fasting and postprandial blood samples. Multivariable linear regression analyses were performed to assess the associations of α-TOH metabolites and measures of glucose homeostasis. We included 498 participants (45% men) with mean (SD) age of 55.8 (6.1) years who did not use glucose-lowering medication. While blood α-TOH was not associated with measures of glucose homeostasis, urinary oxidized metabolites (α-TLHQ-SO3/GLU) were associated with HOMA-IR and Matsuda index. For example, a one-SD higher α-TLHQ-SO3 was associated with 0.92 (95% CI: 0.87, 0.97) fold lower HOMA-IR and 1.06 (1.01, 1.11) fold higher Matsuda index, respectively. Similar results were obtained for the urinary α-TLHQ to α-CEHC ratio as a measure of oxidized-over-enzymatic conversion of α-TOH. Higher urinary levels of oxidized α-TOH metabolites as well as higher oxidized-to-enzymatic α-TOH metabolite ratio, but not circulating α-TOH or enzymatic metabolites, were associated with lower insulin resistance. Rather than circulating α-TOH, estimates of the conversion of α-TOH might be informative in relation to health and disease.

Formation of \u03b1-tocopherol hydroperoxide and \u03b1-tocopheroxyl radical: relevance for photooxidative stress in Arabidopsis

Tocopherols, lipid-soluble antioxidants play a crucial role in the antioxidant defense system in higher plants. The antioxidant function of α-tocopherol has been widely studied; however, experimental data on the formation of its oxidation products is missing. In this study, we attempt to provide spectroscopic evidence on the detection of oxidation products of α-tocopherol formed by its interaction with singlet oxygen and lipid peroxyl radical. Singlet oxygen was formed using photosensitizer rose bengal and thylakoid membranes isolated from Arabidopsis thaliana. Singlet oxygen reacts with polyunsaturated fatty acid forming lipid hydroperoxide which is oxidized by ferric iron to lipid peroxyl radical. The addition of singlet oxygen to double bond carbon on the chromanol head of α-tocopherol forms α-tocopherol hydroperoxide detected using fluorescent probe swallow-tailed perylene derivative. The decomposition of α-tocopherol hydroperoxide forms α-tocopherol quinone. The hydrogen abstraction from α-tocopherol by lipid peroxyl radical forms α-tocopheroxyl radical detected by electron paramagnetic resonance. Quantification of lipid and protein hydroperoxide from the wild type and tocopherol deficient (vte1) mutant Arabidopsis leaves using a colorimetric ferrous oxidation-xylenol orange assay reveals that α-tocopherol prevents formation of both lipid and protein hydroperoxides at high light. Identification of oxidation products of α-tocopherol might contribute to a better understanding of the protective role of α-tocopherol in the prevention of oxidative damage in higher plants at high light.

A Lesson Learnt from Food Chemistry—Elevated Temperature Triggers the Antioxidant Action of Two Edible Isothiocyanates: Erucin and Sulforaphane

In this communication we demonstrate that two natural isothiocyanates, sulforaphane (SFN) and erucin (ERN), inhibit autoxidation of lipids at 140 °C but not below 100 °C. This effect is due to thermal decomposition of ERN and SFN to sulfenic acids and methylsulfinyl radicals, species able to trap lipidperoxyl radicals. Our observations shed new light on thermal processing of vegetables containing these two isothiocyanates.