ascorbic-acid and hydroquinone

Examine clinical trials performed for depigmenting agents in order to determine the most effective and well-tolerated depigmenting agent.. We searched clinical trials, published and unpublished, performed for hydroquinone, ascorbic acid, azelaic acid, retinol and niacinamide in the period 2009 till present. Studies were examined based on participant information, design, duration, intervention, outcome measurements and statistical significance.. Sixty-one studies were examined, 40 published and 21 unpublished. Design, outcome measures and intervention showed sources of bias were not avoided. Only 30% of published trials were double-blind, 27% used a placebo and 80% used subjective measurements for their results. Unpublished trials follow similar outcomes, however, did not provide any significant results.. Based on these results, we are unable to recommend a safer, more effective depigmenting agent. Lack of thorough trials limits us from accepting depigmenting agent full evaluation. To accept a depigmenting agent, its duration must test for long-term safety, clinical trial must be double-blind and comparative, use participants of the correct skin type and measure outcomes objectively. In addition, lack of results for parallel unpublished studies leaves room for discussion. Efforts toward creating more effective formulations are welcomed.

Topics: Ascorbic Acid; Clinical Trials as Topic; Dicarboxylic Acids; Double-Blind Method; Humans; Hydroquinones; Niacinamide; Patient Safety; Research Design; Skin Lightening Preparations; Skin Pigmentation; Vitamin A

Effective cosmetic surgery depends on proper preparation of the skin prior to the procedure, excellent wound care, and an appropriate postoperative skin maintenance program. Accomplishing this goal requires a thorough understanding of topical agents. Substances applied to the skin can alter barrier function, permeability, transepidermal water loss, immune response, wound repair, vasostability, collagen deposition, epidermal turnover, and melanin formation, to name a few. Each of these skin characteristics can affect the quality of the end surgical result. This article discusses topical agents used in association with cosmetic surgery.

Topics: Administration, Topical; Adolescent; Adult; Aged; Ascorbic Acid; Carotenoids; Chemexfoliation; Dicarboxylic Acids; Female; Humans; Hydroquinones; Hydroxy Acids; Keratolytic Agents; Male; Middle Aged; Postoperative Care; Preoperative Care; Retinoids; Salicylates; Skin Aging; Skin Care; Skin Pigmentation; Sunscreening Agents; Surgery, Plastic; Vitamin A; Vitamin E

A common, disfiguring problem in women, melasma is often refractory to treatment, and long-term remissions are difficult to achieve. This study assessed the safety and effectiveness of a procedure combining microdermabrasion, a topical regimen, and low fluence Q-switched Nd:YAG laser treatment.. In this observational study of 27 female subjects, phototypes II-V, referred for treatment of mixed-type melasma refractory to previous therapies, low-fluence QS Nd:YAG laser treatment of 1.6-2 J/cm(2) with 5 or 6 mm spot was administered immediately following microdermabrasion. Daily application of a broad-spectrum sunscreen began immediately; subjects used a topical skin care regimen of hydroquinone with tretinoin or vitamin C. Treatments were repeated at 4-week intervals. Follow-up assessment was done 3-12 months after the last treatment. Adverse effects were recorded at each visit. Standardized digital photographs obtained before each treatment session and at follow-up visits were objectively assessed by blinded comparison using a quartile grading system.. Treatment was successful in all skin types, deemed painless by all subjects, and required no anesthesia. Average number of treatments was 2.6. Twenty-two subjects (81%) had >75% clearance of melasma; 11 subjects (40%) achieved >95% clearance. Most subjects showed >50% clearance of their melasma 1 month after the first treatment. Side effects were limited to mild post-treatment erythema, which developed after the microdermabrasion and lasted approximately 30-60 minutes. Four subjects noted temporary exacerbation of melasma after inadvertent sun exposure, but this resolved within several weeks of resuming the topical skin care regime. Remission lasted at least 6 months.. Microdermabrasion plus low-fluence QS Nd:YAG laser treatment is a simple, non-invasive procedure with minimal risk, no recovery time, and long-lasting remission. Treatment works on all skin phototypes in just two to three treatment sessions. Subject compliance with skin care was excellent, probably due to the dramatic improvement observed within 4 weeks.

Topics: Adult; Antioxidants; Ascorbic Acid; Combined Modality Therapy; Dermabrasion; Female; Follow-Up Studies; Humans; Hydroquinones; Keratolytic Agents; Lasers; Lasers, Solid-State; Melanosis; Middle Aged; Single-Blind Method; Sunscreening Agents; Treatment Outcome; Tretinoin

A 4% hydroquinone/10% L-ascorbic acid treatment system aims to treat early signs of photodamage in normal to oily skin and help prevent further photodamage. The system also contains vitamin E, witch hazel, aloe barbadensis leaf juice, penetration-enhancing ingredients, micronized zinc oxide, and octinoxate.. Patients with minimal or mild facial photodamage and hyperpigmentation, and normal to oily facial skin, used the treatment system for 12 weeks.. Of 34 females enrolled, 30 completed. Median scores for the overall integrated assessment of photodamage, overall intensity of pigmentation, fine lines and wrinkles, tactile roughness, and laxity were significantly improved at week 12 compared with baseline. Furthermore, ≥ 90 percent of patients considered their skin was smoother, softer, more evenly toned, and more radiant, and 100 percent were satisfied with the overall appearance of their skin.. The treatment system can help to ameliorate early signs of photodamage in normal to oily skin.

Topics: Adult; Ascorbic Acid; Dermatologic Agents; Drug Combinations; Female; Follow-Up Studies; Humans; Hydroquinones; Hyperpigmentation; Patient Satisfaction; Sebum; Severity of Illness Index; Skin Aging; Skin Care; Treatment Outcome

Melasma is an acquired treatment-resistant hyperpigmentation of the skin.. Sixteen women with idiopathic melasma were included in our trial. After randomization by another clinician, they were instructed to use, at night, 5% ascorbic acid cream on one side of the face and 4% hydroquinone cream on the other side, for 16 weeks. Sunscreen was applied daily throughout the period of observation. They were evaluated every month by colorimetry, digital photography, and regular color slides. Subjective evaluation by each patient was also taken into account.. The best subjective improvement was observed on the hydroquinone side with 93% good and excellent results, compared with 62.5% on the ascorbic acid side (P < 0.05); however, colorimetric measures showed no statistical differences. Side-effects were present in 68.7% (11/16) with hydroquinone vs. 6.2% (1/16) with ascorbic acid.. Although hydroquinone showed a better response, ascorbic acid may play a role in the therapy of melasma as it is almost devoid of side-effects; it could be used alone or in combination therapy.

Topics: Administration, Topical; Adult; Ascorbic Acid; Dermatologic Agents; Double-Blind Method; Female; Humans; Hydroquinones; Melanosis; Treatment Outcome

Although an aggressive use of tretinoin along with hydroquinone enables an efficient treatment of hyperpigmented skin lesions, irritant dermatitis remains to be solved.. To evaluate the efficiency and adverse effects of 10% all-trans retinol (ROL) gel for improvement of skin hyperpigmentation.. Ten-percent ROL gel was used instead of 0.1% tretinoin gel in our two-phased bleaching protocol (bleaching and healing phases); 5% hydroquinone and 7% lactic acid ointment were used along with ROL gel in the bleaching phase (2 to 6 weeks). Five-percent hydroquinone and 7% ascorbic acid ointment were used alone during the healing phase (4 to 6 weeks). Twenty-one Japanese patients with hyperpigmented lesions on the face were enrolled in this study, and 18 patients who were followed for more than 10 weeks were analyzed.. Improvement of pigmentation was seen in 16 of 18 patients after an average treatment period of 11.3 weeks, and in 6 patients, pigmentation was almost eliminated after treatment. Erythema and scaling were seen, however, during the bleaching phase as well as the bleaching treatment with tretinoin gel.. ROL can improve skin hyperpigmentation to a similar extent to tretinoin when used at high concentration, whereas it induces irritant dermatitis as well.

Topics: Adult; Aged; Ascorbic Acid; Dermatitis, Irritant; Drug Therapy, Combination; Erythema; Female; Gels; Humans; Hydroquinones; Hyperpigmentation; Lactic Acid; Middle Aged; Treatment Outcome; Vitamin A

Melasma, also known as mask of pregnancy, is a common, acquired hypermelanosis seen in women with Fitzpatrick skin types II-V, and is often recalcitrant to treatment with depigmentation agents. Glycolic acid has been added to hydroquinone formulations in the past to enhance their depigmentation effects, but may cause irritation, leading to postinflammatory hyperpigmentation.. To assess the safety and efficacy of a cream containing 4% hydroquinone, 10% buffered glycolic acid, vitamins C and E, and sunscreen (Glyquin, ICN Pharmaceuticals, Costa Mesa, USA) vs. a cream containing sunscreen alone in the depigmentation of epidermal melasma of the face.. Thirty-nine Hispanic women, Fitzpatrick skin types III-V, with bilateral epidermal melasma were enrolled in a randomized controlled trial lasting 12 weeks. Patients underwent twice-daily full-face application with the study cream or with the cream containing sunscreen only. Changes in pigmentation were measured using a mexameter, the melasma area and severity index (MASI), and a global evaluation by the patient and blind investigator. Safety evaluations were performed at each follow-up visit.. Thirty-five patients completed the trial. Irritation was more common with the study cream, but resolved with temporary cessation of cream application and the addition of moisturizers. Mexameter results demonstrated a significant decrease in the degree of pigmentation using the study cream compared with the cream containing sunscreen alone (P < 0.0001). Fifteen of 20 patients (75%) using the study cream improved, whereas only two of 15 patients (13%) improved using sunscreen alone.. A cream containing 4% hydroquinone, 10% buffered glycolic acid, vitamins C and E, and sunscreen is safe and effective in the treatment of melasma.

Topics: Administration, Cutaneous; Adult; Ascorbic Acid; Drug Therapy, Combination; Female; Glycolates; Humans; Hydroquinones; Keratolytic Agents; Melanosis; Severity of Illness Index; Sunscreening Agents; Treatment Outcome; Vitamin E

Hydroquinone (HQ) is used as a depigmenting agent. In this work we demonstrate that tyrosinase hydroxylates HQ to 2-hydroxyhydroquinone (HHQ). Oxy-tyrosinase hydroxylates HQ to HHQ forming the complex met-tyrosinase-HHQ, which can evolve in two different ways, forming deoxy-tyrosinase and p-hydroxy-o-quinone, which rapidly isomerizes to 2-hydroxy-p-benzoquinone or on the other way generating met-tyrosinase and HHQ. In the latter case, HHQ is rapidly oxidized by oxygen to generate 2-hydroxy-p-benzoquinone, and therefore, it cannot close the enzyme catalytic cycle for the lack of reductant (HHQ). However, in the presence of hydrogen peroxide, met-tyrosinase (inactive on hydroquinone) is transformed into oxy-tyrosinase, which is active on HQ. Similarly, in the presence of ascorbic acid, HQ is transformed into 2-hydroxy-p-benzoquinone by the action of tyrosinase; however, in this case, ascorbic acid reduces met-tyrosinase to deoxy-tyrosinase, which after binding to oxygen, originates oxy-tyrosinase. This enzymatic form is now capable of reacting with HQ to generate p-hydroxy-o-quinone, which rapidly isomerizes to 2-hydroxy-p-benzoquinone. The formation of HHQ during the action of tyrosinase on HQ is demonstrated by means of high performance liquid chromatography mass spectrometry (HPLC-MS) by using hydrogen peroxide and high ascorbic acid concentrations. We propose a kinetic mechanism for the tyrosinase oxidation of HQ which allows us the kinetic characterization of the process. A possible explanation of the cytotoxic effect of HQ is discussed.

Topics: Ascorbic Acid; Biocatalysis; Hydrogen Peroxide; Hydroquinones; Hydroxylation; Kinetics; Molecular Structure; Monophenol Monooxygenase; Skin Lightening Preparations

Literature data are scarce on the activities of analogous pairs of hydrophilic and lipophilic antioxidants related to the 'polar paradox' distinguishing antioxidants based on their partitioning between lipids and water. The peroxidation of linoleic acid (LA) in the presence of either Cu(II) ions alone or Cu(II) ions combined with Trolox (TR), ascorbic acid (AA), hydroquinone (HQ) and gallic acid (GA), as hydrophilic antioxidants, or with α-tocopherol (TocH), ascorbyl palmitate (AP), tert-butyl hydroquinone (TBHQ) and propyl gallate (PG), as their respective lipophilic analogues, was investigated in aerated and incubated emulsions at 37 °C and pH 7.. LA peroxidation induced by Cu(II) followed pseudo-first-order kinetics with respect to the formation of primary (hydroperoxides) and secondary (aldehyde- and ketone-like) oxidation products, which were determined by ferric thiocyanate (Fe(III)-SCN) and thiobarbituric acid-reactive substances (TBARS) methods respectively. With the exception of TocH at certain concentrations, the tested compounds showed antioxidant behaviour depending on their polarities. The results were evaluated in the light of structure-activity relationships and the polar paradox.. The results of this study partly confirm the hypothesis that the polar paradox experiences limitations in oil-in-water emulsions and that its validity is also dependent on the concentrations of the antioxidants employed.

Topics: alpha-Tocopherol; Antioxidants; Ascorbic Acid; Chromans; Copper; Emulsions; Gallic Acid; Hydrophobic and Hydrophilic Interactions; Hydroquinones; Iron; Kinetics; Linoleic Acid; Lipid Peroxidation; Peroxides; Propyl Gallate; Structure-Activity Relationship; Thiobarbituric Acid Reactive Substances; Thiocyanates

A redox active polymer, hydroquinone modified chitosan (Q-chitosan) was synthesized and characterized by IR and (1)H NMR spectroscopy. The nanocomposite of Q-chitosan with carbon was prepared and used to construct a stable conductive film on the electrode surface. The SEM studies confirms that the Q-chitosan/C composite covers the electrode surface with polymer embedded 50 nm size carbon particles. The formal redox potential, E(0) of the Q-chitosan/C composite modified electrode is evaluated to be 0.09 V vs. Ag/AgCl at pH 7 and the composite electrode shows an excellent electrocatalytic activity toward the ascorbic acid (AA) at 0.0 V vs. Ag/AgCl. It is more negative potential than the similar AA biosensors and the lower potential oxidation of AA enabled the selective detection of AA over major interferences such as dopamine and uric acid. Using amperometric method, the linear range for ascorbic acid is estimated to be 10 μM to 5 mM with the detection limit of 3 μM and the sensitivity is 0.07 6μA μM(-1)cm(-2).

Topics: Ascorbic Acid; Biosensing Techniques; Carbon; Chitosan; Hydroquinones; Microelectrodes; Nanocomposites; Polymers

Skin pigmentation is a multistep process of melanin synthesis by melanocytes, its transfer to recipient keratinocytes and its degradation. As dyspigmentation is a prominent marker of skin ageing, novel effective agents that modulate pigmentation safely are being sought for both clinical and cosmetic use. Here, a number of plant extracts were examined for their effect on melanogenesis (by melanin assay and Western blotting) and melanin transfer (by confocal immunomicroscopy of gp100-positive melanin granules in cocultures and by SEM analysis of filopodia), in human melanocytes and in cocultures with phototype-matched normal adult epidermal keratinocytes. Mulberry, Kiwi and Sophora extracts were assessed against isobutylmethylxanthine, hydroquinone, vitamin C and niacinamide. Compared with unstimulated control, all extracts significantly reduced melanogenesis in human melanoma cells and normal adult epidermal melanocytes. These extracts also reduced melanin transfer and reduced filopodia expression on melanocytes, similar to hydroquinone and niacinamide, indicating their effectiveness as multimode pigmentation actives.

Topics: 1-Methyl-3-isobutylxanthine; Actinidia; Ascorbic Acid; Cells, Cultured; Coculture Techniques; Fruit; Humans; Hydroquinones; Keratinocytes; Melanins; Melanocytes; Microscopy, Confocal; Morus; Niacinamide; Plant Extracts; Plant Leaves; Plant Roots; Sophora

Electrospray ionization (ESI) involves the dispersion of a liquid containing analytes of interest into a fine aerosol by applying a high potential difference to the sample solution with respect to a counter electrode. Thus, from the electrochemical point of view, the ESI source represents a two-electrode controlled-current electrochemical flow cell. The electroactive compounds part of the solvent sprayed may be altered by occurring electrolysis (oxidation in positive ion mode and reduction in negative ion mode). These reactions can be troublesome in the context of unknown identification and quantification. In the search for a simple, inexpensive, and efficient way to suppress electrochemical oxidation in positive ESI, the usability of ascorbic acid, hydroquinone, and glutathione for homogenous redox buffering was tested. Performance of the antioxidants was assessed by analyzing pharmaceutical compounds covering a broad range of functional groups prone to oxidation. Different emitter setups were applied for continuous infusion, flow injection, and liquid chromatography/mass spectrometry experiments. Best performance was obtained with ascorbic acid. In comparison to hydroquinone and glutathione, ascorbic acid offered superior antioxidant activity, a relatively inert oxidation product, and hardly any negative effect on the ionization efficiency of analytes. Furthermore, ascorbic acid suppressed the formation of sodiated forms and was able to induce charge state reduction. Only in the very special case of analyzing a compound isobaric to ascorbic acid, interference with the low-abundant [ascorbic acid+H](+) signal may become a point of attention.

Topics: Antioxidants; Ascorbic Acid; Buffers; Equipment Design; Glutathione; Hydroquinones; Oxidation-Reduction; Pharmaceutical Preparations; Spectrometry, Mass, Electrospray Ionization

Described in this work is the kinetics of oxidation of ascorbic acid and hydroquinone by a tetranuclear Mn(IV) oxidant, [Mn(4)(μ-O)(6)(bipy)(6)](4+) (1(4+), bipy =2,2(/)-bipyridine), in aqueous solution over a wide pH range 1.5-6.0. In particular, below pH 3.0, protonation on the oxo-bridge of 1(4+) results in the formation of [Mn(4)(μ-O)(5)(μ-OH)(bipy)(6)](5+) (1H(5+)) as an additional oxidant over 1(4+). Both ascorbic acid and ascorbate whereas only hydroquinone and none of its protolytic species were found to be reactive reducing agents in these reactions. Analysis of the rate data clearly established that the oxo-bridge protonated oxidant 1H(5+) is kinetically far more superior to 1(4+) in oxidizing ascorbic acid and hydroquinone. Rates of these reactions are substantially lowered in D(2)O-enriched media in comparison to that in H(2)O media. An initial one electron one proton transfer electroprotic rate step could be mechanistically conceived. DFT studies established that among the two sets of terminal and central Mn(IV) atoms in the tetranuclear oxidant, one of the two terminal Mn(IV) is reduced to Mn(III) at the rate step that we can intuitively predict considering the probable positive charge distribution on the Mn(IV) atoms.

Topics: Ascorbic Acid; Hydroquinones; Manganese; Molecular Structure; Organometallic Compounds; Oxidation-Reduction; Quantum Theory; Water

We report a new reusable electrochemical array for parallel biamperometric measurements that has been designed for use with standard microplates. The 48-channel array uses half of the available 96 wells and has 48 pairs of Pt wire electrodes. Applications to the quantitation of a variety of oxidizable species, including acetaminophen, ascorbic acid, hydroquinone, trolox, and uric acid, are demonstrated in assays that use potassium ferricyanide as an oxidant to produce a mixture of ferri- and ferrocyanide. Hydrogen peroxide quantitation is also demonstrated, based on an assay in which ferrocyanide is oxidized, again to produce a mixture of ferri- and ferrocyanide. Detection limits (signal-to-noise ratio (S/N) = 3) in these assays range from 1 (acetaminophen, R2 = 0.994) to 8 microM (ascorbic acid, R2 = 0.967), and linearity was observed to analyte concentrations of at least 100 microM. We also demonstrate the application of the biamperometric array to enzymatic assays, using the glucose oxidase reaction as an example; following a 20 min enzyme reaction time, a detection limit of 0.1 mM glucose was obtained. These results indicate that applications to other oxidase-based assays are feasible in this high-throughput format. The new electrochemical array employs standard, inexpensive microplates, and the biamperometric measurements are simple, precise, and rapid, requiring only 2 min for 48 parallel measurements.

Topics: Acetaminophen; Ascorbic Acid; Calibration; Chromans; Electrochemistry; Electrodes; Ferrocyanides; Glucose; Glucose Oxidase; Hydrogen Peroxide; Hydroquinones; Microchemistry; Oxidation-Reduction; Platinum; Uric Acid

The photolysis of lumichrome, riboflavin, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) was studied in air-saturated aqueous solution at room temperature in the presence of appropriate electron donors: ascorbic acid, aromatic amino acids or amines, e.g. ethylenediaminetetraacetate (EDTA). The overall reaction is conversion of oxygen via the hydroperoxyl/superoxide radical into hydrogen peroxide. The quantum yield of oxygen uptake increases with the donor concentration, e.g. up to 0.3 for riboflavin, FMN or FAD in the presence of EDTA or ascorbic acid (0.3-10mM). The formation of H(2)O(2) is initiated by quenching of the acceptor triplet state by the electron donor and subsequent reaction of the semiquinone radical with oxygen. Specific properties of flavins are discussed including the radicals involved and the pH and concentration dependences. The quantum yield of photodegradation is low under air, but substantial under argon, where the major product absorbing in the visible spectral range is the corresponding hydroquinone.

Topics: Air; Amines; Amino Acids; Ascorbic Acid; Electrons; Flavins; Hydroquinones; Oxygen; Photolysis; Solutions; Water

Ointments of the skin depigmentation agent hydroquinone (HQ) have been prepared by extemporaneous nonsterile compounding in our hospital. The HQ ointments were highly effective in the treatment of various types of skin pigmentations; however, various problems have emerged including chromatic aberration of the ointments, a relatively large variability of efficacy, and mild topical side effects including irritation. In this paper, the cytotoxicity of HQ was assessed in vitro using rat skin fibroblasts as the concentration with 50% survival after 24 h exposure to be 16.5 microM. The intradermal concentrations at 2 h after application of the HQ ointments was also estimated to be 358 mM and 51.7 mM in stratum corneum and viable tissue (viable epidermis+dermis), respectively, by an in vitro rat skin permeation study with rat full-thickness abdominal skin and Franz-type diffusion cells. It was demonstrated that the intradermal concentration of HQ was much higher than that eliciting cytotoxicity, suggesting that the topical side effects after application of HQ ointment were due to the cytotoxicity of HQ.

Topics: Animals; Antioxidants; Ascorbic Acid; Cell Survival; Cells, Cultured; Colorimetry; Diffusion; Fibroblasts; Hydroquinones; Male; Ointments; Rats; Rats, Wistar; Skin; Skin Absorption; Sulfates

Polymer gels whose NMR and optical properties change when irradiated offer unique advantages for measuring radiation dose distributions. To date, all acrylic polymer gel dosimeters must be manufactured, stored and irradiated in hypoxic conditions which severely limits their use and stability. A new formulation of acrylic dosimeter gel has been developed that responds well in normal atmosphere and which we have named MAGIC (Methacrylic and Ascorbic acid in Gelatin Initiated by Copper). To produce dosimeter gels, an aqueous solution of gelatin, open to the atmosphere, is mixed with methacrylic acid, copper(II) ions, ascorbic acid and hydroquinone. It is believed that the copper(II) and ascorbic acid form a complex with oxygen which (with radiolysis of water) serves as a free radical source for the initiation of the polymerization of methacrylic acid. At room air the water proton spin relaxation rate R2 in MAGIC gels is proportional to absorbed dose though the precise relationship depends on the composition of the gel and the initiating complex. For example, in the range 0-30 Gy the slope of the response of R2 versus dose at 20 MHz was 0.300, 0.519 and 0.681 s(-1) Gy(-1), respectively, when the concentration of MAA was 3, 6 and 9%. The slopes increased to 0.310, 0.567 and 0.868 s(-1) Gy(-1) at 85 MHz. An important determinant of the sensitivity to detect small dose changes is shown to be the slope-to-intercept ratio of the dose-response curve. These varied from 0.08 to 0.17, comparable to hypoxic gels described earlier. MAGIC gels can be manufactured and used much more easily than the previous formulations and can be imaged by magnetic resonance imaging or optical scanning, and thus they will likely be of considerable interest to radiation physicists.

Topics: Ascorbic Acid; Copper; Dose-Response Relationship, Radiation; Gelatin; Gels; Hydroquinones; Ions; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Methacrylates; Phantoms, Imaging; Polymers; Pressure; Protons; Radiometry

Some chemical and fungicidal effects of 20 phthalocyanines of Co, Fe, Cu, and Al were studied. Under dark conditions, these complexes reduced nitroblue tetrazolium in the presence of KCN, accelerated the autoxidation of ascorbate or hydroquinone and decomposed hydrogen peroxide. In the later reaction, hydroxyl radical was generated as evidenced with the deoxyribose assay. The inhibition by superoxide dismutase and catalase of catalyzed autoxidation of ascorbate suggests the participation of superoxide anion-radical and hydrogen peroxide in the reaction. Most complexes were toxic to the fungus Magnaporthe grisea which causes blast disease of rice. The toxicity was enhanced by light being diminished by antioxidant reagents sequestering active oxygen species. Some complexes (including nontoxic ones), after 1-day contact with a leaf surface of the disease-susceptible rice cultivar, induced the fungitoxicity of leaf diffusate. This toxicity was also light-activated and sensitive to antioxidant reagents. Several complexes, when added to inocula, decreased 2-3 times the frequency of the compatible symptoms of the blast. It is suggested that in planta, the dark redox activity of phthalocyanines along with their photosensitization promote the generation of active oxygen, which damages the parasite and, therefore, favors disease resistance.

Topics: Antioxidants; Ascorbic Acid; Catalysis; Dose-Response Relationship, Drug; Fungicides, Industrial; Hydrogen Peroxide; Hydroquinones; Hydroxyl Radical; Indoles; Light; Magnaporthe; Metals; Organometallic Compounds; Oryza; Oxidation-Reduction; Plant Diseases; Plant Leaves; Superoxides; Toxicity Tests

A steady-state kinetics of peroxidase cooxidation of ascorbic acid and hydroquinone catalyzed by horseradish peroxidase was studied. Ascorbic acid and hydroquinone were shown to be oxidized successively, and hydroquinone promoted the oxidation of ascorbic acid. Excess ascorbic acid inhibited peroxidase in the cooxidation of the substrates at pH 5-7. The values of catalytic constants, (kcat, K(m), and Ka) were determined. A possible activation mechanism of the peroxidation of ascorbic acid in the presence of hydroquinone was suggested, and its biological significance was considered.

Topics: Ascorbic Acid; Horseradish Peroxidase; Hydroquinones; Kinetics; Oxidation-Reduction; Spectrophotometry, Ultraviolet

Hydroquinone is a well known reagent used in the treatment of pigmentation disorders. The instability of the quinones and the required active concentration make topical treatment rather difficult. We tested the efficacy of an ascorbate-phytohydroquinone complex that inhibits the synthesis of melanin and promotes the degradation of the existing melanin. Lentigo senile lesions were evaluated before and after 1 month of treatment. Objective skin color evaluation was performed instrumentally. After one month of treatment, a clear depigmentation of the macules was measured. None of the volunteers reported any side effects from the prolonged treatment with the hydroquinone containing product.

Topics: Administration, Cutaneous; Aged; Aged, 80 and over; Apiaceae; Ascorbic Acid; Benzoyl Peroxide; Citrus; Colorimetry; Dermatologic Agents; Drug Combinations; Female; Follow-Up Studies; Glucosides; Humans; Hydroquinones; Lentigo; Male; Melanins; Middle Aged; Oils, Volatile; Oxyquinoline; Plant Extracts; Skin Pigmentation

The generation of hydroxyl radicals (.OH) from the reaction of Cu(II) complexes with biological reductants such as ascorbic acid, glutathione, acetylcysteine, and hydroquinone was confirmed by spin-trapping experiments using electron spin resonance (ESR). The following Cu(II) complexes were used: Cu(II)-(CyHH)2 (CyHH, cyclo(L-histidyl-L-histidyl)), Cu(II)(OP)2 (OP, o-phenanthroline), Cu(II)(HGG) (HGG, L-histidyl-glycylglycine), and Cu(II)(en)2 (en, ethylenediamine). The methyl radical adduct of alpha-(pyridyl-4-N-oxide)-N-tert-butylnitrone (POBN-CH3) was obtained from the reaction of ascorbic acid with all Cu(II) complexes used here in the presence of a spin trap, POBN, and dimethyl sulfoxide, indicating the generation of .OH. Glutathione, N-acetylcysteine, and hydroquinone reacted with both Cu(II)(CyHH)2 and Cu(II)(OP)2 to generate POBN-CH3, while these reductants did not react with either Cu(II)(HGG) or Cu(II)(en)2. Interestingly, the formation of POBN-CH3 in the reaction of Cu(II)-(CyHH)2 with glutathione or N-acetylcysteine was found only at a Cu(II)(CyHH)2/glutathione or Cu(II)(CyHH)2/N-acetylcysteine ratio of 1. The DNA strand scission caused by reaction mixtures of Cu(II) complexes with reductants was investigated under the same conditions as the ESR spin-trapping experiments. Addition of ascorbic acid to mixtures of these four Cu(II) complexes and DNA resulted in DNA strand breakage. Hydroquinone plus Cu(II)(CyHH)2 also caused DNA strand scission. In addition, DNA strand breakage was observed with the reaction of Cu(II)(OP)2 with glutathione, N-acetylcysteine, and hydroquinone. In contrast, reaction mixtures of glutathione, N-acetylcysteine, or hydroquinone with Cu(II)-(HGG) or Cu(II)(en)2 did not cause DNA strand scission within the concentration range used. The results obtained here suggest that there is a good correlation between POBN-CH3 formation and DNA strand scission. Thus, DNA strand scission may be caused by .OH generated from the reaction of some Cu(II) complexes with biological reductants under aerobic conditions. Since ascorbic acid, glutathione, and N-acetylcysteine are present in living cells, some Cu(II) complexes may be capable of initiating DNA damage in the presence of these reductants.

Topics: Acetylcysteine; Ascorbic Acid; Copper; DNA Damage; Electron Spin Resonance Spectroscopy; Glutathione; Hydrogen Peroxide; Hydroquinones; Hydroxyl Radical; Oxidation-Reduction; Plasmids; Reactive Oxygen Species; Reducing Agents; Spin Trapping

Acylated derivatives of ascorbic acid were found to be active in a number of biochemical and physiological processes. In the present study we investigated the effects of 6-O-palmitoyl ascorbate on collagen synthesis by cultured foreskin human fibroblasts. Our observations indicate a marked stimulatory effect on collagen synthesis by 6-O-palmitoyl ascorbate in the concentration range of 5-20 microM, while the synthesis stimulated by ascorbic acid was maximal at concentrations of 20-100 microM. Cells treated with 10 microM palmitoyl ascorbate for 36 h exhibited a production of collagen threefold greater than those in the presence of 10 microM ascorbic acid, and it was about the same as in cells treated with 100 microM ascorbic acid. By 48 h differences were not significant. Acylated ascorbate impaired vitality of the treated fibroblasts at concentrations exceeding 20 microM in media supplemented with 0.5% FCS. However, most of the cytotoxic effect was neutralized by FCS at a concentration of 10%. The resistance of acylated ascorbate against oxidative degradation as well as the role of free radicals in the modulation of collagen synthesis by ascorbic acid and by its derivatives is discussed.

Topics: Acylation; Antioxidants; Ascorbate Oxidase; Ascorbic Acid; Cells, Cultured; Collagen; Deferoxamine; DNA; Dose-Response Relationship, Drug; Fibroblasts; Humans; Hydroquinones; Oxidation-Reduction; Serum Albumin, Bovine; Skin; Time Factors

Topics: Ascorbic Acid; Basidiomycota; Calorimetry; Catechols; Enzymes, Immobilized; Food Analysis; Hydroquinones; Laccase; Oxidoreductases; Substrate Specificity; Thermodynamics

Our goal was to characterize possible species and strain differences in the hepatic microsomal biotransformation of 1,4-dichlorobenzene (1,4-DCB). Experiments compared extent of labeled 1,4-DCB conversion to oxidized metabolites, glutathione conjugates, and covalently bound metabolites by hepatic microsomes from humans, from male B6C3F1 mice, and from males of three rat strains (Fischer 344, Sprague-Dawley (SD), and Wistar). These rodents were selected for comparison because of their dissimilar responses to 1,4-DCB, notably, hepatocarcinogenicity in the B6C3F1 mouse but not the Wistar or Fischer rat, and nephrotoxicity and carcinogenicity in the Fischer rat. The species rank order for total in vitro conversion of 1,4-DCB was mouse > rat >> human. Conversion by microsomes from Fischer and Wistar rats was similar, whereas SD rats showed less biotransformation than the other two strains. Microsomes from the mouse produced most of the reactive metabolites as indicated by covalent binding to macromolecules (>20% of total metabolites formed). This covalent binding by mouse microsomes was extensively inhibited by ascorbic acid (AA), with a concomitant increase in hydroquinone formation, indicating an important role for benzoquinones as reactive metabolites. Phenobarbital pretreatment of rats enhanced the in vitro conversion of 1,4-DCB and the amount of covalent binding. Covalent binding for all rat microsomes was partly (33-79%) inhibited by AA. Addition of glutathione (GSH) plus AA further diminished the covalent binding with concomitant increased formation of the GSH-conjugated epoxide. Human microsomes produced the least reactive metabolites, with the majority (>70%) of this covalent binding prevented by GSH addition. The observed species differences, notably the more pronounced biotransformation of 1,4-DCB to reactive species including benzoquinones, could be factors in this compound's liver carcinogenicity in B6C3F1 mice but not other rodent species.

Topics: Animals; Ascorbic Acid; Binding, Competitive; Biotransformation; Carcinogens; Chlorobenzenes; Chromatography, High Pressure Liquid; Cytochrome P-450 Enzyme System; Glutathione; Humans; Hydroquinones; Insecticides; Isotope Labeling; Male; Mice; Microsomes, Liver; Mutagens; Phenobarbital; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Rats, Wistar; Species Specificity

Many studies describe the protective role of vitamin C (ascorbic acid) against cancer development and in treatment of established cancer. The present study investigated whether ascorbic acid demonstrates a therapeutic benefit for prostate cancer.. Androgen-independent (DU145) and androgen-dependent (LNCaP) human prostate cancer cell lines were both treated in vitro with vitamin C (0-10 mM). Cell counts, cell viability, and thymidine incorporation into DNA were determined.. Treatment of DU145 and LNCaP cells with vitamin C resulted in a dose- and time-dependent decrease in cell viability and thymidine incorporation into DNA. Vitamin C induced these changes through the production of hydrogen peroxide; addition of catalase (100-300 units/ml), an enzyme that degrades hydrogen peroxide, inhibited the effects of ascorbic acid. Superoxide dismutase, an enzyme that dismutates superoxide and generates hydrogen peroxide, did not prevent decreases in cell number and DNA synthesis, suggesting further the involvement of hydrogen peroxide in vitamin C-induced changes. These results clearly indicate that reactive oxygen species (ROS) are involved in vitamin C-induced cell damage. However, that singlet oxygen scavengers such as sodium azide and hydroquinone and hydroxyl radical scavengers such as D-mannitol and DL-alpha-tocopherol did not counteract the effects of ascorbic acid on thymidine incorporation suggests that vitamin C-induced changes do not occur through the generation of these ROS.. Vitamin C inhibits cell division and growth through production of hydrogen peroxide, which damages the cells probably through an as yet unidentified free radical(s) generation/mechanism. Our results also suggest that ascorbic acid is a potent anticancer agent for prostate cancer cells.

Topics: Androgens; Antineoplastic Agents; Ascorbic Acid; Azides; Cell Count; Cell Survival; DNA, Neoplasm; Dose-Response Relationship, Drug; Free Radicals; Humans; Hydrogen Peroxide; Hydroquinones; Hydroxyl Radical; In Vitro Techniques; Male; Prostatic Neoplasms; Sodium Azide; Superoxide Dismutase; Thymidine; Tritium; Tumor Cells, Cultured

Horseradish peroxidase (HRP) was oxidized by IrCl6(2-) to a mixture of compounds I and II, the rate of oxidation and the ratio of the mixture being greatly affected by pH (Hayashi & Yamazaki, 1979). Oxidation of HRP by IrCl6(2-) in the presence of fluoride was significantly accelerated. This resulted in the formation of a new compound which is a ferric fluoride complex containing a porphyrin pi-cation radical. The spectrum of the new compound showed a decreased absorption band in the Soret region and a broad band at 570 nm; which was converted to that of the original ferric fluoride complex by addition of ascorbate or hydroquinone. Addition of cyanide slowed down the oxidation of HRP by IrCl6(2-), and the oxidation product was the same as that obtained in the absence of cyanide. Compound I was formed when H2O2 was added to HRP in the presence of fluoride or cyanide. The one-electron reduction potential (Eo') of the oxidized HRP-fluoride complex was measured at several pH values, the Eo' value at pH 7 being 861 +/- 4 mV. The ratio of delta Eo' to delta pH was 49 mV/pH unit.

Topics: Ascorbic Acid; Fluorides; Free Radicals; Horseradish Peroxidase; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydroquinones; Iridium; Oxidation-Reduction; Porphyrins; Potassium Cyanide; Sodium Fluoride; Spectrophotometry

Lipid peroxidation in vitro homogenates of brain was examined as sequela of lead toxicity. The levels of malondialdehyde (MDA) in homogenates of rat brain (1 ml, 5% w/v) treated with lead (50 micrograms) alone or in combination with ascorbic acid (100 micrograms), alphatocopherol (100 micrograms) or hydroquinone (100 micrograms) were evaluated. The levels of MDA were consistently evoked by lead in a dose-related manner. The toxicity of lead was further advanced by the action of the pro-oxidant drug ascorbic acid on the brain. However, the anti-oxidant drugs alphatocopherol and hydroquinone decreased the toxic effect of lead on the brain. These results clearly show that the enhanced lipid peroxidation may provide a basis of lead-induced neurotoxicity.

Topics: Animals; Ascorbic Acid; Brain; Drug Interactions; Hydroquinones; Lead; Lipid Peroxidation; Malondialdehyde; Rats; Vitamin E

At neutral pH, compound I of Arthromyces ramosus peroxidase (ARP) was stable and was reduced to ferric ARP without apparent formation of compound II upon titration with ascorbate or hydroquinone. In the titration experiments, compound II was seen as an intermediate only at alkaline pH. However, measuring a difference spectrum in the Soret region by a stopped-flow method, we found that compound II was formed during the catalytic oxidation of ascorbate even at neutral pH. Using an EPR spectrometer with a microflow system, we measured the steady-state concentration of benzosemiquinone formed in the ARP-catalyzed oxidation of hydroquinone. The results clearly showed that ARP catalyzes the oxidation of hydroquinone by a one-electron-transfer mechanism, as does horseradish peroxidase. These observations led to the conclusion that compound I is reduced to compound II through a one-electron reduction by ascorbate or hydroquinone. Therefore, we concluded that ARP compound II is unusually unstable and is rapidly reduced to ferric enzyme without accumulation in the titration experiment. The unusual instability of ARP compound II is explained in terms of the high reduction potential of compound II. The reduction potentials (E0') of compounds I and II were measured at several pH values from redox equilibria with potassium hexachloroiridate on the basis of E0' = 0.90 V for the IrCL6(2)-IrCl6(3)- couple. These values were determined to be 0.915 and 0.982 V at pH 7, respectively, and decreased with increasing pH. This pH dependence was markedly changed by the buffer concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Ascorbic Acid; Catalysis; Electron Spin Resonance Spectroscopy; Enzyme Stability; Hydrogen-Ion Concentration; Hydroquinones; Mitosporic Fungi; Oxidation-Reduction; Peroxidase

Electrodes modified by the electrodeposition of poly(3-methylthiophene) were used as chemical sensors for some organic and biological molecules of industrial and medicinal interest. The electrochemical behaviors of ferri/ferrocyanide, catechol, ascorbic acid, hydroquinone, dopamine epinephrine, acetaminophen, p-aminophenol and NADH were examined by cyclic voltammetry. The results showed that the proposed modified surface catalyzes the oxidation of these compounds. Differential pulse and square wave techniques were used for the analysis of binary mixture of ascorbic acid with catechol, NADH, dopamine and p-aminophenol. Voltammetric peak resolution was also demonstrated for a ternary mixture of ascorbic acid, catechol and p-aminophenol. Polymer coated electrode was also used in an amperometric detector for flow injection analysis of most of the aforementioned compounds. The responses of the polymer electrode were 4-10 times larger as compared to those of platinum. The modified electrode displayed excellent response stability for successive injections and detection limits were 10 ppb for catechol, dopamine, epinephrine, NADH and p-aminophenol, 1 ppb for acetaminophen and 100 ppb for ascorbic acid. Voltammetric peak positions were affected by the nature of the electrolyte and its pH. Also, film thicknesses were shown to be a factor affecting both the current magnitudes and oxidation peak potential of NADH.

Topics: Acetaminophen; Aminophenols; Ascorbic Acid; Biosensing Techniques; Catechols; Dopamine; Electrochemistry; Epinephrine; Hydroquinones; Iron; NAD; Polymers; Thiophenes

Potential second-stage modifying effects of 8 antioxidants on lung tumorigenesis initiated by N-bis(2-hydroxypropyl)nitrosamine (DHPN) were examined in male F344 rats. After an initial 2-week treatment with DHPN (0.1% in drinking water), rats were administered one of the antioxidants supplemented in the diet for 30 weeks. Although the incidences of lung adenomas were not affected, those of carcinomas were lowered by 2% butylated hydroxyanisole (BHA, 2 rats/20 rats), 1% butylated hydroxytoluene (BHT, 1/20), 0.8% ethoxyquin (EQ, 3/20) and 1% a-tocopherol (a-TP, 2/20) treatments as compared to the control level (9/20), while 5% sodium L-ascorbate (SA), 0.8% catechol (CC), 0.8% resorcinol (RN), and 0.8% hydroquinone (HQ) did not exert any significant effect on incidence. Quantitative analysis of adenomas and carcinomas (numbers and areas of lesions per unit area of lung section) revealed obvious inhibitory effects of SA, CC, and RN as well as BHA, BHT, EQ, and a-TP. Among the antioxidants, BHT exerted the strongest inhibitory activity. In contrast, DHPN-induced thyroid tumorigenesis was significantly enhanced by BHT (14/20) and EQ (20/20) treatments (control = 5/20). Thus the antioxidants showed opposite effects on lung and thyroid carcinogenesis in the rat.

Topics: Adenoma; Animals; Antioxidants; Ascorbic Acid; Body Weight; Butylated Hydroxyanisole; Butylated Hydroxytoluene; Carcinoma; Catechols; Ethoxyquin; Hydroquinones; Kidney Neoplasms; Lung Neoplasms; Male; Nitrosamines; Organ Size; Rats; Rats, Inbred F344; Resorcinols; Thyroid Neoplasms; Urinary Bladder Neoplasms; Vitamin E

Inhibition or stimulation of melanogenesis have been found to occur as a result of the alteration of hydroquinone levels in the body. Substances which stimulate melanogenesis are found to lower the level of hydroquinone in amphibia, and evidence for the relationship is also given by mammalian experiments.

Topics: Animals; Ascorbic Acid; Bufonidae; Ficusin; Hydroquinones; Liver; Male; Melanins; Muridae; Rats; Rats, Inbred Strains; Skin

A delay in the onset of accumulation of methylene hexadecanoic acid could be engendered in Pseudomonas denitrificans growing under limited oxygen conditions when the concentration of citrate but not the concentration of succinate in the medium was increased from 0.1 to 0.5%. Ascorbate, which specifically reduced a cytochrome component possessing a maximum absorbance at 551 nm, partially inhibited the accumulation of methylene hexadecanoic acid under conditions which otherwise led to maximal production. Limiting terminal cytochrome oxidase activity by controlling the oxygen supply, or by the use of low concentrations of the oxidase inhibitors cyanide or azide also prevented the accumulation of the fatty acid regardless of the nature or concentration of carbon source in the medium. Measurement of the levels of ATP, NAD and NADH as well as the steady state of reduction of respiratory components in vivo showed that the onset of accumulation of methylene hexadecanoic acid could be specifically correlated with the state of reduction of respiratory components. The uniqueness of succinate respiration in promoting the synthesis of cyclopropane synthetase (unsaturated-phospholipid methyltransferase (EC 2.1.1.16) under limited oxygen conditions could therefore be assigned to the high degree of oxidation of respiratory components observed under this condition.

Topics: Ascorbic Acid; Cyclopropanes; Fatty Acids; Hydroquinones; Methionine; Methyltransferases; NAD; Oxidation-Reduction; Oxygen Consumption; Pseudomonas

Topics: Ascorbic Acid; Catechol Oxidase; Humans; Hydroquinones; Oxidation-Reduction; Oxidoreductases; Phenols; Vitamins