ascorbic-acid and quinone

In aqueous solutions containing ascorbic acid and O

Topics: Ascorbic Acid; Hydrogen Peroxide; Oxidation-Reduction; Quinones; Superoxides

Our study proposes a pharmacological strategy to target cancerous mitochondria via redox-cycling "mitocans" such as quinone/ascorbate (Q/A) redox-pairs, which makes cancer cells fragile and sensitive without adverse effects on normal cells and tissues. Eleven Q/A redox-pairs were tested on cultured cells and cancer-bearing mice. The following parameters were analyzed: cell proliferation/viability, mitochondrial superoxide, steady-state ATP, tissue redox-state, tumor-associated NADH oxidase (tNOX) expression, tumor growth, and survival. Q/A redox-pairs containing unprenylated quinones exhibited strong dose-dependent antiproliferative and cytotoxic effects on cancer cells, accompanied by overproduction of mitochondrial superoxide and accelerated ATP depletion. In normal cells, the same redox-pairs did not significantly affect the viability and energy homeostasis, but induced mild mitochondrial oxidative stress, which is well tolerated. Benzoquinone/ascorbate redox-pairs were more effective than naphthoquinone/ascorbate, with coenzyme Q0/ascorbate exhibiting the most pronounced anticancer effects in vitro and in vivo. Targeted anticancer effects of Q/A redox-pairs and their tolerance to normal cells and tissues are attributed to: (i) downregulation of quinone prenylation in cancer, leading to increased mitochondrial production of semiquinone and, consequently, superoxide; (ii) specific and accelerated redox-cycling of unprenylated quinones and ascorbate mainly in the impaired cancerous mitochondria due to their redox imbalance; and (iii) downregulation of tNOX.

Topics: Adenosine Triphosphate; Animals; Ascorbic Acid; Mice; Neoplasms; Oxidation-Reduction; Quinones; Superoxides

Topics: Benzoquinones; Catalytic Domain; Computer Simulation; Cyclooxygenase Inhibitors; Lipoxygenase Inhibitors; Molecular Docking Simulation; Oxidation-Reduction; Resorcinols; Spectrum Analysis; Structure-Activity Relationship

Antioxidants have gained marked attention owing to their ability to prevent the oxidation of biological components and to protect the body from reactive oxygen species, thereby maintaining human health. Thus, antioxidant-rich dietary supplements and natural foods can be effective against oxidative stress and can even act as chemopreventive agents. Therefore, a simple and rapid assay for evaluation of antioxidant capacity and assessment of their distribution profile in natural sources is vital. Herein, we report a rapid, innovative chemiluminescence (CL) platform for evaluation and visualization of antioxidant capacity. We found that intense and long-lasting CL was formed upon the redox reaction of quinones, e.g., menadione, with antioxidants, e.g., l-ascorbic acid, in the presence of luminol. The produced CL intensities were proportional to the antioxidants' concentrations with a detection limit of 0.18 μM for the model antioxidant, l-ascorbic acid. As the formed CL was long-lasting, it could be easily captured and detected with a charge-coupled device (CCD) camera. To evaluate the quantification ability of the CCD camera, we developed a smart and fast microplate-based assay based on photographing the generated CL with a cooled CCD camera. The photographed CL intensities were linearly proportional with the antioxidant concentrations, and then the method was applied for photographing multiple food sample extracts. Ultimately, we utilized our method for the distribution profiling of antioxidant capacity in food cut sections. Samples were dipped in luminol and then in quinone, followed by CCD camera photography, without the need for any pulverization/extraction procedure, giving precise antioxidant distribution information.

Topics: Antioxidants; Ascorbic Acid; Benzoquinones; Humans; Luminescent Measurements; Luminol; Molecular Structure; Tissue Distribution

Cigarette smoke (CS) is the strongest risk factor for emphysema. However, the mechanism of the disease is not clear. One reason is that each puff of CS is a complex mixture of approximately 4,000 chemicals, and it is yet to be known which of these chemical(s) are directly involved in the pathogenesis of lung injury in emphysema. The purpose of this study was to demonstrate that p-benzoquinone (p-BQ) produced in the lungs of CS-exposed guinea pigs is a causative factor for destruction of alveolar cells resulting in emphysema that is prevented by vitamin C. Vitamin C-restricted guinea pigs were subjected to whole-body CS exposure from five Kentucky research cigarettes (3R4F) per day or intramuscular injection of p-BQ in amounts approximately produced in the lung from CS exposure with and without oral supplementation of vitamin C. Progressive exposure of CS or p-BQ treatment caused progressive accumulation of p-BQ in the lung that was accompanied by destruction of alveolar cells and emphysema. The pathogenesis involved was arylation, oxidative stress, inflammation, and apoptosis. Vitamin C (30 mg/kg body weight/d), a potential antagonist of p-BQ, prevented accumulation of p-BQ in the lung and the pathogenesis of emphysema. Our study provides the first proof that inactivation of p-BQ, a causative factor of emphysema in CS-exposed lung, could constitute a novel and effective approach in the prevention of emphysema. We consider that a moderately high dose of vitamin C may be a simple preventive therapy for emphysema in chronic smokers.

Topics: Animals; Apoptosis; Ascorbic Acid; Benzoquinones; Disease Models, Animal; Guinea Pigs; Inflammation; Oxidative Stress; Pulmonary Alveoli; Pulmonary Emphysema; Smoke; Smoking

Cardiovascular disease (CVD) remains one of the major killers in modern society. One strong risk factor of CVD is cigarette smoking that causes myocardial injury and leads to the genesis of pathological cardiovascular events. However, the exact toxic component(s) of cigarette smoke (CS) and its molecular and cellular mechanisms for causing myocardial injury leading to heart damage and its prevention are largely unknown.. Using a guinea pig model, here we show that chronic exposure to CS produces myocardial injury that is prevented by vitamin C. Male guinea pigs were fed either vitamin C-deficient (0.5 mg/day) or vitamin C-sufficient (15 mg/day) diet and subjected to CS exposure from 5 Kentucky Research cigarettes (3R4F)/day (6 days/week) in a smoke chamber up to 8 weeks. Pair-fed sham controls were subjected to air exposure instead of CS exposure under similar conditions. Myocardial injury was produced in CS-exposed marginal vitamin C-deficient guinea pigs as evidenced by release of cardiac Troponin-T and I in the serum, oxidative stress, inflammation, apoptosis, thrombosis and collagen deposition in the myocardium. Treatment of rat cardiomyocyte cells (H9c2) in vitro and guinea pigs in vivo with p-benzoquinone (p-BQ) in amounts derived from CS revealed that p-BQ was a major factor responsible for CS-induced myocardial damage. A moderately large dose of vitamin C (15 mg/day) prevented CS/p-BQ-induced myocardial injury. Population based studies indicated that plasma vitamin C levels of smokers without disease were significantly lower (p = 0,0000) than that of non-smokers. Vitamin C levels of CS-related cardiovascular patients were further lower (p = 0.0000) than that of smokers without disease.. The results indicate that dietary supplementation of vitamin C may be a novel and simple therapy for the prevention of pathological cardiovascular events in habitual smokers.

Topics: Adult; Aged; Animals; Apoptosis; Ascorbic Acid; Benzoquinones; Disease Progression; Enzyme Activation; Guinea Pigs; Humans; Inflammation; Male; Matrix Metalloproteinases; Middle Aged; Myocardial Infarction; Myocardium; Myocytes, Cardiac; Neutrophil Infiltration; Oxidative Stress; Rats; Smoking

Increasing evidence has demonstrated that EGCG possesses prooxidant potential in biological systems, including modifying proteins, breaking DNA strands and inducing the generation of reactive oxygen species. In the present study, the prooxidant effect of EGCG on erythrocyte membranes was investigated. SDS-PAGE and NBT-staining assay were utilized to detect the catechol-protein adducts that generated upon treating the membranes with EGCG. The results indicated that EGCG was able to bind covalently to sulfhydryl groups of membrane proteins, leading to the formation of protein aggregates with intermolecular cross-linking. We suggested that the catechol-quinone originated from the oxidation of EGCG acted as a cross-linker on which peptide chains were combined through thiol-S-alkylation at the C2- and C6-sites of the gallyl ring. EGC showed similar effects as EGCG on the ghost membranes, whereas ECG and EC did not, suggesting that a structure with a gallyl moiety is a prerequisite for a catechin to induce the aggregation of membrane proteins and to deplete membrane sulfhydryls. EDTA and ascorbic acid inhibited the EGCG-induced aggregation of membrane proteins by blocking the formation of catechol-quinone. The information of the present study may provide a fresh insight into the prooxidant effect and cytotoxicity of tea catechins.

Topics: Ascorbic Acid; Benzoquinones; Catechin; Cell Membrane; Cross-Linking Reagents; Edetic Acid; Erythrocytes; Flavonoids; Humans; Membrane Proteins; Molecular Weight; Phenols; Polyphenols; Protein Multimerization; Protein Structure, Quaternary; Reactive Oxygen Species; Sulfhydryl Compounds; Tea

This laboratory experiment was carried out at the Department of Agricultural Technology, Mahasarakham University, Northeast Thailand during July and August 2008. The experiment aimed to determine an effective natural organic acid that would delay the unattractive skin browning of santol fruit, while at the same time not damaging the quality of the fruit. The experiment included a study of the fruit's polyphenol oxidase (PPO) activity, phenolic content and quinone content, as they relate to colour and a study of total soluble solid content, pH, titratable acidity and vitamin C content as they relate to fruit quality. A Completely Randomized Design (CRD) with four replications was used. Each replication consisted of 10 fruits. Santol fruit was harvested at 145 days after full bloom and dipped for 30 min in aqueous solutions of two organic acids that were used as treatments, i.e., 0% for T1 (control), 5% citric acid for T2, 5% ascorbic acid for T3, 10% citric acid for T4 and 10% ascorbic acid for T5 and stored at room temperature (28 degrees C, 90% R.H.) to investigate the effect of the acid on fruit weight, skin colour, PPO activity and other internal parameters. The results showed that the most appropriate anti-browning agent for santol fruit was found with T2. It gave the highest mean values, 57.37 and 55.95, of brightness (L*) at 4 and 10 Days After Storage (DAS), respectively. In addition, PPO activity of flesh tissue was lowest for T2 with mean values of 0.0078 to 0.0092 by 0 and 300 S, respectively. The phenolic content in the flesh tissue significantly increased with an increase in numbers ofDAS, whereas the reverse was found with the pH level in the fruits. They were lowest for T2, with mean values of 6.00, by 10 DAS. There were no significant differences among the treatments in any of the measured Total Soluble Solids (TSS), Titratable Acidity (TA) and vitamin C content.

Topics: Ascorbic Acid; Benzoquinones; Catechol Oxidase; Crops, Agricultural; Food Handling; Food Preservation; Fruit; Hydrogen-Ion Concentration; Meliaceae; Phenols; Thailand

2-euryfuryl- and 2-euryfuryl-3-nitro-1,4-benzoquinone Q2 and Q3, prepared via oxidative coupling reactions of sesquiterpene euryfuran 1 to 2-nitro-1,4-benzoquinone and 1,4-benzoquinone, were tested for their cytotoxicity towards TLT cells (a murine hepatoma cell line) in the absence and in the presence of vitamin C. Their cytotoxic profile was completely different. In cells incubated with Q2 (from 1 to 50 microg/ml), cell survival was not modified, both GSH and ATP were depleted to about 50% of control values (at 50 microg/ml); and caspase-3 was activated in a dose-dependent manner. These effects were observed whatever cells were incubated or not in the presence of vitamin C. In the case of Q3, the cytotoxicity was rather unrelated to its concentration but the association of vitamin C plus the highest Q3 concentration (50 microg/ml) results in a strong cell death (more than 60%). At such a concentration, a complete lack of caspase-3 activity was observed, probably due to cell lysis. At lower concentrations of Q3 (1 and 10 microg/ml), caspase-3 activity was lower than that observed in the absence of vitamin C or even under control conditions. Both GSH and ATP were kept fairly constant as compared to control values but in the presence of vitamin C and Q3, at 50 microg/ml, a decrease in their amounts was observed.

Topics: Adenosine Triphosphate; Animals; Antineoplastic Agents; Ascorbic Acid; Benzoquinones; Carcinoma, Hepatocellular; Caspase 3; Cell Death; Cell Line, Tumor; Cell Survival; Cytoplasm; Enzyme Activation; Glutathione; Intracellular Space; L-Lactate Dehydrogenase; Mice

Formation of oxyradicals under UV-B stress was investigated using cucumber cotyledons. UV-B radiation induced production of free radicals which were analyzed by ESR spectroscopy. Evidence was obtained for the formation of superoxide and hydroxyl radicals in the tissues by comparing PBN-adducts formed with radicals obtained by chemical autooxidation of KO2 and Fenton's reaction. Addition of superoxide dismutase (SOD) to the reaction mixture partially reduced the intensity of signals confirming the production of superoxide radical as well as hydroxyl radicals. These radicals were quenched in vitro by the natural antioxidants alpha-tocopherol, ascorbic acid and benzoquinone. Changes in the level of antioxidants were also monitored under UV-B stress. The endogenous level of ascorbic acid was enhanced and alpha-tocopherol level was reduced in the tissue after exposure to UV-B radiation. The present report happens to be the first direct evidence obtained for the formation of superoxide and hydroxyl radicals in plant tissues exposed to UV-B radiation.

Topics: alpha-Tocopherol; Antioxidants; Ascorbic Acid; Benzoquinones; Cotyledon; Cucumis sativus; Electron Spin Resonance Spectroscopy; Hydroxyl Radical; Oxidation-Reduction; Oxidative Stress; Superoxide Dismutase; Superoxides; Ultraviolet Rays

The quinones 1,4-naphthoquinone (NQ), methyl-1,4-naphthoquinone (MNQ), trimethyl-1,4-benzoquinone (TMQ) and 2,3-dimethoxy-5-methyl-1,4-benzoquinone (UQ-0) enhance the rate of nitric oxide (NO) reduction by ascorbate in nitrogen-saturated phosphate buffer (pH 7.4). The observed rate constants for this reaction were determined to be 16+/-2,215+/-6,290+/-14 and 462+/-18 M-1 s-1, for MNQ, TMQ, NQ and UQ-0, respectively. These rate constants increase with an increase in quinone one-electron redox potential at neutral pH, E1(7). Since NO production is enhanced under hypoxia and under certain pathological conditions, the observations obtained in this work are very relevant to such conditions.

Topics: Ascorbic Acid; Benzoquinones; Naphthoquinones; Nitric Oxide; Nitrogen Oxides; Nitrous Oxide; Oxidation-Reduction

Topics: 4-Hydroxyphenylpyruvate Dioxygenase; Alkaptonuria; Antioxidants; Ascorbic Acid; Benzoquinones; Cyclohexanones; Enzyme Inhibitors; Homogentisic Acid; Humans; Nitrobenzoates; Oxidation-Reduction

Redox cycling is believed to be the most general molecular mechanism of quinone (Q) cytotoxicity. Along with redox cycling induced by a reductase, a similar process is known to occur via electron transfer from ascorbate (AscH-) to Q with formation of a semiquinone radical (Q.-): (1) Q + AscH- (k1)--> Q.- + Asc.- + H+ (2) Q.- + O2 --> Q + O2.-. The net effect of reactions (1) and (2) provides for the catalytic oxidation of AscH-, with Q serving as a catalyst. In this work, the kinetics of oxygen consumption accompanying this process were studied with several substituted 1,4-benzoquinones (BQ) at 37 degrees C in phosphate buffer, pH 7.40, using the Clark electrode technique. The value of k1 determined from the initial rate of oxygen consumption was typically found to increase when the one-electron reduction potential E(Q/Q.-) shifted to more positive values. With Q, for which E(Q/Q.-) is less than -100 mV, the rate of oxygen uptake (R(OX)) was found to be directly correlated with the [Q][AscH-] value independent of the concentration of individual reagents, remaining constant for a long period. With mono- and dialkyl-substituted 1,4-BQs, for which E(Q/Q.-) is higher than -100 mV, significant deviations from the above simple kinetic regularities were observed. In particular, R(OX) decreased dramatically with time and critical phenomena (the existence of certain concentrations of Q and/or AscH- above or below which the catalytic oxidation of AscH- ceased completely after a non-stationary period of short duration) were observed. These abnormalities can be explained on the basis of the kinetic scheme which contains, in addition to reactions (1) and (2), several side reactions including that between Q.- and AscH-. Implications of critical phenomena discovered in this study for the problems of Q toxicity and vitamin C avitaminosis are discussed.

Topics: Ascorbic Acid; Benzoquinones; Computer Simulation; Kinetics; Oxidation-Reduction; Oxygen; Quinones

The present study shows that MP8 in the presence of H2O2 is able to catalyze the rupture of the stable carbon-fluorine bond of 4-fluorophenol, used as a model substrate for the oxidative dehalogenation reaction. 1,4-Benzoquinone was shown to be the primary reaction product. It is also demonstrated that there was significant [18O] incorporation into the product, 1,4-benzoquinone, from 18O-labelled H2(18)O but not from H2(18)O2. This implies that water participates in the reaction mechanism, and acts as a source for the oxygen atom inserted into the product. It also suggests that the reaction is not a result of direct oxygen transfer from H2O2 through the heme catalyst to the product. Furthermore, ascorbic acid, known to efficiently block MP8-catalyzed peroxidase-type conversions, inhibits the MP8-dependent dehalogenation reaction, most likely because of its ability to reduce the phenoxy radical back to the parent substrate. This observation together with the above-mentioned incorporation of oxygen from the solvent into the benzoquinone product indicates that MP8 dehalogenates 4-fluorophenol and converts it to 1,4-benzoquinone in a peroxidase- and not a P-450-type of reaction mechanism. Overall, our results indicate that the oxidative dehalo genation of para-halogenated phenols, resulting in the formation of benzoquinones, is not specific only for cytochrome P-450 enzymes. Hemoproteins exhibiting peroxidase activity could also play a role in the metabolism of these xenobiotics, resulting in the formation of electrophilic reactive benzoquinone type metabolites.

Topics: Animals; Ascorbic Acid; Benzoquinones; Catalysis; Chromatography, High Pressure Liquid; Fluorobenzenes; Gas Chromatography-Mass Spectrometry; Horseradish Peroxidase; Horses; Hydrogen Peroxide; Isotope Labeling; Magnetic Resonance Spectroscopy; Male; Microsomes, Liver; Myocardium; Oxidation-Reduction; Oxygen Isotopes; Peroxidases; Phenols; Rats; Rats, Wistar; Water

Inhibition of electron transport in broken chloroplasts by DBMIB, under light-limiting conditions, is shown to be bypassed by PMS in a manner similar to the known effects of the phenylenediamine derivatives TMPD and DAD. These bypasses were demonstrated and further studied by modulated fluorimetry, monitoring DBMIB inhibition by the shift of the steady-state fluorescence towards the Fm level and the release of inhibition by a reverse shift together with establishment of a quenching effect by background far-red light. Comparative studies were also made with electron transport blocked by DCMU or BNT. A weak bypass by TMPD and a weaker one by PMS of the block created by DCMU was observed by modulated fluorimetry. The block created by BNT is similarly shown to be bypassed by TMPD but hardly or not at all by PMS. Bypass effects persisted even in the presence of ascorbate. It appears that, following reduction of the different cofactors by ascorbate in the stroma side, illumination caused the accumulation of a pool of oxidized cofactor molecules in the lumen, which is able to mediate electron transport between reduced plastoquinone and plastocyanin or P-700. The existence and the size of this pool were found to depend largely on the internal pH at the lumen, presenting an artificial system in which electron flow is controlled by the lumenal pH. The bypassing electron transport in the presence of DBMIB presumably avoids the participation of the cytochrome b6f complex. During its occurrence, there is also a strong imbalance in the activities of the two photosystems for linear electron flow, in favor of PS II. These experiments may thus serve to establish an in vitro model system for a future investigation of effects related to changes in the imbalance between the two photosystems and its regulation. Furthermore, this experimental system may also be utilized to study the role of the internal lumenal pH in control of photosynthesis.

Topics: Ascorbic Acid; Benzoquinones; Chloroplasts; Electron Transport; Fluorometry; Gramicidin; Kinetics; Oxygen

The copper-chelating thiol drug diethyldithiocarbamate protected isolated hepatocytes from benzoquinone-induced alkylation cytotoxicity by reacting with benzoquinone and forming a conjugate which was identified by fast atom bombardment mass spectrometry as 2-(diethyldithiocarbamate-S-yl) hydroquinone. In contrast to benzoquinone, the conjugate was not cytotoxic to isolated hepatocytes. The thiol reductant dithiothreitol had no effect on benzoquinone-induced alkylation cytotoxicity. However, inactivation of catalase in the hepatocytes with azide and addition of the reducing agent ascorbate markedly enhanced the cytotoxicity of the conjugate but did not affect benzoquinone-induced cytotoxicity. Furthermore, inactivation of glutathione reductase and catalase in hepatocytes greatly enhanced the cytotoxicity of the conjugate and caused oxidation of GSH to GSSG. The conjugate also stimulated cyanide-resistant respiration, which suggests that the conjugate undergoes futile redox cycling resulting in the formation of hydrogen peroxide which causes cytotoxicity in isolated hepatocytes only if the peroxide detoxifying enzymes are inactivated. Diethyldithiocarbamate does, however, protect uncompromised isolated hepatocytes from benzoquinone cytotoxicity by conjugating benzoquinone, thereby preventing the electrophile from alkylating essential macromolecules. Diethyldithiocarbamate therefore changed the initiating cytotoxic mechanism of benzoquinone from alkylation to oxidative stress, which was less toxic.

Topics: Animals; Ascorbic Acid; Benzoquinones; Catalase; Cell Survival; Cells, Cultured; Ditiocarb; Drug Interactions; Kinetics; Liver; Male; Oxidation-Reduction; Rats; Rats, Inbred Strains; Spectrometry, Mass, Fast Atom Bombardment

The effects of ascorbic acid on the excretion of homogentisic acid and its derivative benzoquinone acetic acid were studied in two adults and three infants. The administration of relatively large amounts of ascorbic acid to the adults was followed by a disappearance of benzoquinone acetic acid from the urine, whereas the level of excretion of homogentisic acid did not change. This could have relevance to the pathogenesis of ochronotic arthritis. In the 4-mo-old infant and the 5-mo-old infant ascorbic acid in the urine may have doubled the amount of homogentisic acid, presumably through an effect on the immature p-hydroxyphenylpyruvic acid oxidase. Dietary reduction of the intake of tyrosine and phenylalanine substantially reduced the excretion of homogentisic acid.

Topics: Aged; Alkaptonuria; Ascorbic Acid; Benzoquinones; Homogentisic Acid; Humans; Infant; Male; Middle Aged; Quinones

Topics: Acetates; Ascorbic Acid; Benzoquinones; Humans; Quinones; Urine; Vitamins

Topics: Androstenols; Ascorbic Acid; Benzoquinones; Humans; Rickets; Vitamins