ascorbic-acid and 2-tert-butylhydroquinone

Substantial studies have shown that curcumin, a dietary compound from turmeric, has beneficial effects on many diseases. However, curcumin rapidly degrades at physiological pH, making it difficult to interpret whether the observed actions of curcumin are from curcumin itself or its degradation products. Therefore, it is important to better understand the mechanisms involved in curcumin degradation and the roles of degradation in its biological actions.. Here, we show that a series of redox active antioxidants with diverse chemical structures, including gallic acid, ascorbate (vitamin C), tert-butylhydroquinone (TBHQ), caffeic acid, rosmarinic acid, and Trolox (a water-soluble analog of vitamin E), dramatically increased curcumin stability in phosphate buffer at physiological pH. When treated in basal cell culture medium in MC38 colon cancer cells, curcumin rapidly degraded with a half-life of several minutes and showed a weak antiproliferative effect; co-addition of antioxidants enhanced stability and antiproliferative effect of curcumin. Finally, co-administration of antioxidant significantly increased plasma level of curcumin in animal models.. Together, these studies strongly suggest that a redox-dependent mechanism plays a critical role in mediating curcumin degradation. In addition, curcumin itself, instead of its degradation products, is largely responsible for the observed biological actions of curcumin.

Topics: Animals; Antioxidants; Ascorbic Acid; Caffeic Acids; Cell Line, Tumor; Cell Proliferation; Chromans; Cinnamates; Curcumin; Depsides; Drug Stability; Gallic Acid; Hydrogen-Ion Concentration; Hydroquinones; Male; Mice; Oxidation-Reduction; Rosmarinic Acid

A series of novel l-ascorbyl fatty acid esters were synthesized by catalization of Novozym(®) 435 under ultrasonic irradiation and characterized by infrared spectroscopy, electrospray ionization mass spectra, and nuclear magnetic resonance. Their properties especially antioxidant activity and stability were investigated. The results showed that the reducing power, the scavenging activity of hydroxyl radical and 2,2-diphenyl-1-picrylhydrazyl radical were decreased with the increase of the number of carbon atoms in fatty acid. The hydroxyl radical scavenging activity and reducing power of l-ascorbyl saturated fatty acid esters were better than that of tert-butylhydroquinone. The induction period in lipid oxidation of l-ascorbyl saturated fatty acid esters and tert-butylhydroquinone were longer than that of l-ascorbyl unsaturated fatty acid esters and l-ascorbic acid both in soybean oil and lard. Besides, the l-ascorbyl fatty acid esters showed different stabilities in different conditions by comparing with l-ascorbic acid, and the l-ascorbyl saturated fatty acid esters were more stable than l-ascorbyl unsaturated fatty acid esters in ethanol solution.

Topics: Antioxidants; Ascorbic Acid; Biphenyl Compounds; Dietary Fats; Esters; Fatty Acids; Fatty Acids, Unsaturated; Food Preservatives; Humans; Hydroquinones; Lipase; Lipid Peroxidation; Oxidation-Reduction; Picrates; Soybean Oil; Ultrasonic Waves; Ultrasonics

This study investigated the capacity of various antioxidants in reducing the formation of acrylamide during cookie processing. Five antioxidants, antioxidants of bamboo leaves (AOB), sodium erythorbate (SE), tea polyphenols (TP), vitamin E (VE), and tert-butyl hydroquinone (TBHQ), were individually added into cookie formulas, and acrylamide content was determined by liquid chromatography tandem mass spectrometry (LC-MS/MS). Cookie quality indexes, including flavor, brittleness, and water activity, were also evaluated. Results showed that the maximum inhibitory rate of acrylamide by AOB was achieved with addition of 0.2 g/kg AOB. Addition of AOB (0.2 g/kg), TP (0.1 g/kg), VE (0.1 g/kg), SE (0.1 g/kg), and TBHQ (0.2 g/kg) mitigated the formation of acrylamide by 63.9%, 43.0%, 71.2%, 49.6%, and 54.1%, respectively. Sensory evaluation showed that the color, texture, and flavor of cookies processed with either AOB (0.2 g/kg) or VE (0.1 g/kg) had no significant difference compared to control cookies (P > 0.05). The present study indicated that AOB (0.2 g/kg) and VE (0.1 g/kg) could not only effectively mitigate the formation of acrylamide, but also retain acceptable sensory attributes of cookies. This work shows the potential effectiveness of antioxidants in food processing to decrease acrylamide formation.. There is an urgent need for reducing the level of acrylamide produced during food processing. This study found that certain antioxidants (antioxidant of bamboo leaves and vitamin E) could effectively inhibit acrylamide formation in cookie processing without affecting sensory properties. The results suggested that the application of antioxidants could be an effective method to decrease acrylamide formation.

Topics: Acrylamide; Antioxidants; Ascorbic Acid; Bambusa; Chromatography, Liquid; Color; Female; Food Handling; Humans; Hydroquinones; Male; Plant Leaves; Polyphenols; Tandem Mass Spectrometry; Taste; Tea; Vitamin E

Identification and determination of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), nordihydroguaiaretic acid (NDGA), propyl gallate (PG) and tert-butylhydroquinone (TBHQ) by means of LC/MS and GC/MS were examined. These five phenolic antioxidants were detected as their pseudo-molecular ions [M-H]- by LC/MS using a Shim-pack FC-ODS column with drying gas. Moreover, BHA, BHT and TBHQ were detected based on their mass fragment ions by GC/MS. Decomposition of TBHQ, NDGA and PG during analysis could be prevented by the addition of L-ascorbic acid (AsA) to the extraction solvent. All five antioxidants were extracted from nikuman, olive oils, peanut butter, pasta sauce and chewing gum with a mixture of acetonitrile-2-propanol-ethanol (2:1:1) containing 0.1% AsA (AsA mixture), which had been cooled in a freezer and filtered. One part filtrate and 5 parts water were mixed and placed on a Mega-Bond Elut C18 cartridge, except in the case of chewing gum. Lipids in foods were removed on a C18 cartridge by washing with 5 mL of 5% acetic acid, and antioxidants were eluted with 5 mL of AsA mixture. The antioxidants spiked into nikuman, olive oil, peanut butter, pasta sauce and chewing gum were successfully identified and their concentrations determined by LC/MS, and GC/MS with good recoveries.

Topics: Antioxidants; Ascorbic Acid; Butylated Hydroxyanisole; Butylated Hydroxytoluene; Chromatography, Liquid; Food Analysis; Gas Chromatography-Mass Spectrometry; Hydroquinones; Masoprocol; Mass Spectrometry; Phenols; Propyl Gallate

We describe the synthesis of some 3-tert-butyl-4-hydroxyphenyl D-glycopyranosides by reaction of tert-butylhydroquinone with beta-D-pentaacetyl-glucose, beta-D-pentaacetyl-galactose, 2-acetamido- and 3,4,6-tri-O-acetyl-2-butanamido-2-deoxy-beta-D-glucopyranosyl chlorides as well as the formation of anomeric 3-tert-butyl-4-hydroxyphenyl 4,6-di-O-acetyl-2,3-dideoxy-D-erythro-hex-2-eno-pyranosides by reaction between tert-butylhydroquinone and 3,4,6-tri-O-acetyl-D-glucal. All compounds, except 3-tert-butyl-4-hydroxyphenyl alpha- and beta-D-glucopyranosides, inhibited lipid peroxidation with a degree of potency comparable to that of tert-butyl hydroxyanisole.

Topics: Acetylation; Animals; Antioxidants; Ascorbic Acid; Benzenesulfonates; Glucose; Glycosides; Hydroquinones; Iron; Linoleic Acid; Lipid Peroxidation; Microsomes, Liver; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Rats; Structure-Activity Relationship

We previously showed that the cell-permeant antioxidant 2(3)-tert-butyl-4-hydroxyanisole (BHA) inhibited germinal vesicle breakdown (GVBD) in oocyte-cumulus complexes (OCC) of the rat. The objective of the present studies was to assess other antioxidants and whether such inhibition was reversible. Spontaneous GVBD in OCC incubated for 2 h was significantly inhibited (P < 0.005) by nordihydroguaiaretic acid (NDGA; GVBD = 19.4%), BHA (GVBD = 25.7%), octyl gallate (OG; GVBD = 52.2%), ethoxyquin (EQ; GVBD = 58.8%), 2, 6-di-tert-butyl-hydroxymethyl phenol (TBHMP; GVBD = 59%), butylated hydroxytoluene (BHT; GVBD = 59.5%), and tert-butyl hydroperoxide (TBHP; GVBD = 60.0%). Other antioxidants that produced lower but significant (P < 0.05) inhibition of oocyte maturation included propyl gallate (PG; GVBD = 70.3%), 2,4,5-trihydroxybutrophenone (THBP; GVBD = 71.4%), and lauryl gallate (LG; GVBD = 71.4%). Antioxidants that had no effect on oocyte maturation at the same concentration (100 microM) included ascorbic acid, vitamin E, and Trolox. Inhibition of GVBD was evident for up to 8 h of incubation of OCC and denuded oocytes (DO) with BHA or NDGA and was reversed by washing. NDGA was less potent than BHA for inhibition of GVBD in DO, unlike that seen with OCC. Oocyte maturation was induced by incubation of follicles for 3 h with human chorionic gonadotropin (hCG), and this response was inhibited by BHA or NDGA. These findings support the conclusion that cell-permeant antioxidants inhibit spontaneous resumption of meiosis, which may implicate a role of oxygen radicals in oocyte maturation.

Topics: Animals; Antioxidants; Ascorbic Acid; Butylated Hydroxytoluene; Chorionic Gonadotropin; Chromans; Female; Humans; Hydroquinones; Masoprocol; Meiosis; Oocytes; Ovarian Follicle; Rats; Rats, Sprague-Dawley; Vitamin E

Phenolic antioxidant butylated hydroxyanisole (BHA) is a commonly used food preservative with broad biological activities, including protection against acute toxicity of chemicals, modulation of macromolecule synthesis and immune response, induction of phase II detoxifying enzymes, and especially its potential tumor-promoting activities. Understanding the molecular basis underlying these diverse biological actions of BHA is thus of great importance. Here we demonstrate that BHA is capable of activating distinct mitogen-activated protein kinases (MAPKs), extracellular signal-regulated protein kinase 2 (ERK2), and c-Jun N-terminal kinase 1 (JNK1). Activation of ERK2 by BHA was rapid and transient, whereas the JNK1 activation was relatively delayed and persistent. A major metabolite of BHA, tert-butylhydroquinone (tBHQ), also activated ERK2 but weakly stimulated JNK1 activity. Furthermore, tBHQ activation of ERK2 was late and prolonged, showing a kinetics different from that induced by BHA. ERK2 activation by both compounds required the involvement of an upstream signaling kinase MAPK/ERK kinase (MEK), as evidenced by the inhibitory effect of a MEK inhibitor, PD98059. Pretreatment with N-acetyl-L-cysteine, glutathione, or vitamin E attenuated ERK2 but not JNK1 activation by BHA and tBHQ. Modulation of intracellular H2O2 levels by direct addition of catalase or pretreatment with a catalase inhibitor, aminotriazole, also affected BHA- and tBHQ-stimulated ERK2 activity but not JNK1, indicating the involvement of oxidative stress in the ERK2 activation by these two compounds. However, we did not observe any generation of H2O2 after exposure of cells to BHA or tBHQ using a H2O2-sensitive fluorescent probe, 2',7'-dichlorofluorescein diacetate. Instead, BHA and tBHQ substantially reduced the amount of intracellular H2O2. Furthermore, BHA and tBHQ activation of ERK2 was strongly inhibited by ascorbic acid and a peroxidase inhibitor, sodium azide, suggesting the potential role of phenoxyl radicals and/or their derivatives. Taken together, our results indicate that (i) BHA and its metabolite tBHQ differentially regulate MAPK pathways, and (ii) oxidative stress due to the generation of reactive intermediates, possibly phenoxyl radicals but not H2O2, is responsible for the ERK2 activation by BHA and tBHQ, whereas the JNK1 activation may require a distinct yet unknown mechanism.

Topics: Amitrole; Antioxidants; Ascorbic Acid; Butylated Hydroxyanisole; Calcium-Calmodulin-Dependent Protein Kinases; Catalase; Enzyme Activation; Enzyme Inhibitors; Flavonoids; Flow Cytometry; Free Radical Scavengers; HeLa Cells; Humans; Hydrogen Peroxide; Hydroquinones; Oxidative Stress; Reactive Oxygen Species; Signal Transduction; Tumor Cells, Cultured

The glutathione conjugates of tert-butyl hydroquinone, a metabolite of butylated hydroxyanisole (BHA), possess redox potentials which are much higher as compared to the non-conjugated hydroquinone (0.36 V for the hydroquinone and 1.2-1.4 V for the conjugates). As a result, the redox cycling activity of the conjugates, as measured by oxygen consumption in the presence of a reducing agent, is increased tenfold as compared to the non-conjugated hydroquinone. Since evidence for both oxidative damage and the involvement for glutathione in the toxicity of butylated hydroxyanisole is available, this mechanism may be involved in the toxic action of this compound.

Topics: Animals; Antioxidants; Ascorbic Acid; Butylated Hydroxyanisole; Glutathione; Hydroquinones; Magnetic Resonance Spectroscopy; Male; Microsomes; Molecular Conformation; Molecular Structure; Oxidation-Reduction; Oxygen Consumption; Rats; Structure-Activity Relationship

The proliferation response of rat renal pelvic epithelium, lined by transitional epithelium, to administration of various bladder cancer promoters was investigated. In addition, prostaglandin E2 (PGE2), lipid peroxide (LPO), malondialdehyde (MDA) and cyclic adenosine 3':5'-monophosphate (cyclic AMP) levels were assessed in urine of rats given the non-promoter L-ascorbic acid (AsA) and the promoters sodium L-ascorbate (AsA-Na) or sodium bicarbonate (NaHCO3) for 4 or 8 weeks. DNA synthesis in the renal pelvic epithelium, as assessed by 5-bromo-2'-deoxyuridine (BrdU) incorporation, was increased in the groups given AsA-Na, an extremely high dose of sodium chloride (NaCl), tert-butylhydroquinone (TBHQ) or ethoxyquin (EQ). Moreover, with the exception of AsA-Na, all treatments that induced an elevation of DNA synthesis also caused morphological epithelial alterations as observed by scanning electron microscopy (SEM). Treatment with butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) did not result in any proliferative response of the rat renal pelvis. No treatment-related changes in urinary PGE2 and cyclic AMP were noted, although AsA-Na and AsA but not NaHCO3 reduced levels of LPO and MDA in the urine. The results indicate that while the response of renal pelvic epithelium to certain bladder cancer promoters is similar to that of the bladder itself, none of the urinary cellular growth or free radical biochemical parameters is directly related to urothelial cell proliferation.

Topics: Animals; Ascorbic Acid; Bicarbonates; Butylated Hydroxyanisole; Butylated Hydroxytoluene; Carcinogens; Cyclic AMP; Dinoprostone; DNA; Epithelium; Ethoxyquin; Hydroquinones; Kidney Pelvis; Male; Microscopy, Electron, Scanning; Rats; Rats, Inbred F344; Sodium; Sodium Bicarbonate; Urinary Bladder Neoplasms