ascorbic-acid and idebenone

Chronic sun exposure causes photoaging, the appearance of prematurely aged skin. This phenomenon is characterized by progressive alteration of the dermal extracellular matrix, including elastin and collagen fibers. While many cosmeceuticals claim to improve the appearance of photoaged skin, data are lacking regarding their ability to induce molecular responses associated with wrinkle effacement, particularly increased collagen production.. To conduct a meta-analysis to determine whether there was a factor(s) that could predict response to various cosmeceuticals.. Hundred subjects enrolled in five separate studies of cosmeceuticals containing: L-ascorbic acid, pentapeptide, α-lipoic acid, yeast extract, or 1% idebenone. Five groups consisting of 16-20 volunteers applied one cosmeceutical to their photodamaged forearms for several weeks. Punch biopsies were obtained pretreatment and post-treatment and analyzed for type I procollagen by ELISA.. Analysis of basal collagenesis reinforced the notion that hypo-collagenesis is associated with photoaging severity, independent of age or gender. Treatment outcome varied greatly among subjects, ranging from no improvement to a 7-fold increase in collagenesis. Retrospective statistical meta-analysis was conducted to determine whether age, gender, type of cosmeceutical, or evidence of hypo-collagenesis in untreated skin could predict responsiveness to cosmeceuticals. Our analysis revealed that subjects with hypo-collagenesis responded 6.4 times more often than subjects with normo-collagenesis.. Hypo-collagenesis was the only factor that influenced treatment outcome. This study therefore identifies hypo-collagenesis as the unique parameter predicting anti-aging cosmeceutical treatment outcome. These findings provide a basis for future cosmetic testing and the potential development of custom formula skin care.

Topics: Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Cell Extracts; Cosmetics; Female; Humans; Male; Middle Aged; Procollagen; Protein Biosynthesis; Skin; Skin Aging; Thioctic Acid; Ubiquinone; Yeasts

Reactive oxygen species (ROS) are widely believed to cause or aggravate several human pathologies such as neurodegenerative diseases, cancer, stroke and many other ailments. Antioxidants are assumed to counteract the harmful effects of ROS and therefore prevent or treat oxidative stress-related diseases. In this report, recent human studies exploring the efficiency of antioxidants in prevention and treatment of various diseases are reviewed. Few antioxidants including edaravone (for ischemic stroke in Japan), Nacetylcysteine (for acetaminophen toxicity), alfa-lipoic acid (for diabetic neuropathy) and some flavonoids (polyphenolic compounds present in dietary plants), such as micronized purified flavonoid fraction (diosmin and hesperidin) and oxerutins (for chronic venous insufficiency) as well as baicalein and catechins (for osteoarthritis) have found accepted clinical use. However, despite much enthusiasm in the 1980s and 1990s, many well-known agents such as antioxidant vitamins and also more recently developed compounds such as nitrones have not successfully passed the scrutiny of clinical trials for prevention and treatment of various diseases. This has given rise to a pessimistic view of antioxidant therapy, however, the evidence from human epidemiological studies about the beneficial effects of dietary antioxidants and preclinical in vitro and animal data are compelling. We have probably wasted too much time on agents like antioxidant vitamins instead of focusing on more disease specific, target-directed, highly bioavailable antioxidants. We here discuss possible reasons for the lack of success in some clinical trials and seek to provide some suggestions to be considered if antioxidant therapy is to succeed as an effective therapeutic strategy.

Topics: Acetylcysteine; Animals; Antioxidants; Antipyrine; Ascorbic Acid; Edaravone; Humans; Polyphenols; Thioctic Acid; Ubiquinone; Vitamin A; Vitamin E

Alzheimer's disease is one of the most challenging brain disorders and has profound medical and social consequences. It affects approximately 15 million persons worldwide, and many more family members and care givers are touched by the disease. The initiating molecular event(s) is not known, and its pathophysiology is highly complex. However, free radical injury appears to be a fundamental process contributing to the neuronal death seen in the disorder, and this hypothesis is supported by many (although not all) studies using surrogate markers of oxidative damage. In vitro and animal studies suggest that various compounds with antioxidant ability can attenuate the oxidative stress induced by beta-amyloid. Recently, clinical trials have demonstrated potential benefits from treatment with the antioxidants, vitamin E, selegiline, extract of Gingko biloba, and idebenone. Further studies are warranted to confirm these findings and explore the optimum timing and antioxidant combination of such treatments in this therapeutically frustrating disease.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Animals, Genetically Modified; Antioxidants; Ascorbic Acid; Benzoquinones; Central Nervous System; Central Nervous System Diseases; Clinical Trials as Topic; Drug Therapy, Combination; Free Radicals; Ginkgo biloba; Humans; Lipid Peroxidation; Neuroprotective Agents; Oxidation-Reduction; Phytotherapy; Plants, Medicinal; Selegiline; Ubiquinone; Vitamin E

Patients with Leber hereditary optic neuropathy (LHON) have a progressive decrease of their visual acuity which can deteriorate to <0.1. Some patients can have a partial recovery of their vision in one or both eyes. One prognostic factor associated with a recovery of vision is an early-age onset. The purpose of this study was to determine other clinical factors that are predictive of a good visual recovery.. Sixty-one Japanese LHON patients, with the 11,778 mutation and a mean age of 23.1 ± 12.1 years at the onset, were studied. All patients were initially examined at an acute stage of LHON and were followed for 3 to 10 years. At 1 year after the onset, the lowest visual acuity was <0.1 in all eyes. We studied the following parameters of patients with/without a final visual acuity of ≥ 0.2: sex; heavy consumption of cigarettes and alcohol; taking idebenone; mean age at onset; mean lowest visual acuity; and distribution of the lowest and the final visual acuity.. Fifteen (24.6%) of the 61 patients or 25 (20.5%) of the 122 eyes had a recovery of their visual acuity to ≥ 0.2. The mean age at onset of these 15 patients with visual recovery to ≥ 0.2 was 17.5 ± 7.7 years, and that of the 46 patients without visual recovery to ≥ 0.2 was 25.0 ± 12.8 years (P = 0.02, Mann-Whitney U test). The mean lowest visual acuity of the 25 eyes with visual recovery ≥ 0.2 was 0.04, and that of the 97 eyes without visual recovery to ≥ 0.2 was 0.015 (P < 0.001, Mann-Whitney U test). Fifty percent (15/30) of the eyes whose lowest visual acuity was ≥ 0.04 during 1 year after the onset had a visual recovery to ≥ 0.2, while 11% (10/92) of the eyes whose the lowest visual acuity was ≤ 0.03 had a visual recovery to ≥ 0.2 (P < 0.001, χ. A final visual acuity of ≥ 0.2 was associated with a less severe reduction of the visual acuity at 1 year after the onset. Our findings can be used to predict the visual prognosis in LHON patients.

Topics: Adolescent; Adult; Age of Onset; Aged; Antioxidants; Ascorbic Acid; Child; DNA Mutational Analysis; DNA, Mitochondrial; Female; Follow-Up Studies; Humans; Male; Middle Aged; Optic Atrophy, Hereditary, Leber; Point Mutation; Polymerase Chain Reaction; Prognosis; Recovery of Function; Retrospective Studies; Riboflavin; Ubiquinone; Vision Disorders; Visual Acuity; Visual Field Tests; Vitamin B Complex; Young Adult

Coenzyme Q(10) (CoQ(10)) and its analogs are used therapeutically by virtue of their functions as electron carriers, antioxidant compounds, or both. However, published studies suggest that different ubiquinone analogs may produce divergent effects on oxidative phosphorylation and oxidative stress.. To test these concepts, we have evaluated the effects of CoQ(10), coenzyme Q(2) (CoQ(2)), idebenone, and vitamin C on bioenergetics and oxidative stress in human skin fibroblasts with primary CoQ(10) deficiency. A final concentration of 5 microM of each compound was chosen to approximate the plasma concentration of CoQ(10) of patients treated with oral ubiquinone. CoQ(10) supplementation for one week but not for 24 hours doubled ATP levels and ATP/ADP ratio in CoQ(10) deficient fibroblasts therein normalizing the bioenergetics status of the cells. Other compounds did not affect cellular bioenergetics. In COQ2 mutant fibroblasts, increased superoxide anion production and oxidative stress-induced cell death were normalized by all supplements.. THESE RESULTS INDICATE THAT: 1) pharmacokinetics of CoQ(10) in reaching the mitochondrial respiratory chain is delayed; 2) short-tail ubiquinone analogs cannot replace CoQ(10) in the mitochondrial respiratory chain under conditions of CoQ(10) deficiency; and 3) oxidative stress and cell death can be counteracted by administration of lipophilic or hydrophilic antioxidants. The results of our in vitro experiments suggest that primary CoQ(10) deficiencies should be treated with CoQ(10) supplementation but not with short-tail ubiquinone analogs, such as idebenone or CoQ(2). Complementary administration of antioxidants with high bioavailability should be considered if oxidative stress is present.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Ascorbic Acid; Cells, Cultured; Fibroblasts; Humans; Molecular Structure; Superoxides; Ubiquinone

To ascertain the efficacy of idebenone and multivitamin treatment in Leber's hereditary optic neuropathy (LHON).. Two patients diagnosed of unilateral LHON were treated with megadoses of idebenone, vitamin C and riboflavin for one year. They were examined clinically before, during and after treatment.. No improvement of visual function was observed. Despite the idebenone treatment, in both cases the second eye became involved.. Despite previous reports of visual recovery with idebenone in patients with LHON, our experience shows that an effective treatment for Leber's disease remains to be found.

Topics: Adult; Antioxidants; Ascorbic Acid; Benzoquinones; Female; Humans; Male; Optic Atrophy, Hereditary, Leber; Riboflavin; Treatment Failure; Ubiquinone; Vitamin B Complex; Vitamins

Topics: Antioxidants; Ascorbic Acid; Benzoquinones; Coumaric Acids; Humans; Kinetin; Radiation-Protective Agents; Skin; Ubiquinone; Ultraviolet Rays; Vitamin E

The authors investigated the effectiveness of idebenone combined with vitamin B2 and vitamin C in the treatment of patients with Leber hereditary optic neuropathy (LHON) in an early stage as compared with untreated patients with LHON. These agents may stimulate the formation of ATP.. For this retrospective study, the authors selected 28 outpatients with LHON from the Keio University Hospital. These patients were followed for 2 to 19 years from disease onset. They were divided into two groups: 14 untreated patients (11778 mutation in 10 patients, 3460 mutation in 2 patients, and 14484 mutation in 2 two patients); and 14 treated patients (11778 mutation in 11 patients, 3460 mutation in 1 patient, and 14484 mutation in 2 patients). The treated patients were administered medical treatment with idebenone, vitamin B2, and vitamin C for at least 1 year. The current study evaluated the following: 1) number of eyes with visual recovery > or = 0.3; 2) interval between the onset of LHON and the beginning of visual recovery; 3) interval between the onset of LHON and visual recovery to 0.3; and 4) interval between the beginning of medical treatment and the beginning of visual recovery in the treated subjects.. There was no significant difference in the number of eyes with visual recovery > or = 0.3 in the two groups with the 3460, 11778, or 14484 mutation. Patients with visual recovery showed a fenestrated scotoma or a clearing of central vision. The mean interval between the onset of LHON and the beginning of visual recovery was significantly shorter in the treated group (11.1 months) than in the untreated group (17.4 months) (P = 0.03). The mean interval between the onset of LHON and visual recovery to 0.3 was significantly shorter in the treated group (17.6 months) than in the untreated group (34.4 months) (P = 0.01). The mean interval between the initiation of medical treatment to the beginning of visual recovery was 5.4 months.. Results suggest that the administration of idebenone, vitamin B2, and vitamin C sped the recovery of vision in patients with LHON.

Topics: Adolescent; Adult; Age of Onset; Antioxidants; Ascorbic Acid; Benzoquinones; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mutation; Optic Atrophies, Hereditary; Recovery of Function; Retrospective Studies; Riboflavin; Time Factors; Ubiquinone; Vision Disorders; Visual Acuity

In the present study the effect of ascorbate (0.8 mM)/iron (2.5 microM) on lipid and protein oxidation, in Synaptosomes isolated from rat brain cortex, was evaluated. Vitamin E, idebenone and reduced glutathione were used as free radicals scavengers, in order to analyze the mechanism involved in ascorbate/iron-induced oxidative stress. An increased formation of reactive oxygen species (ROS) in the cytosol and in the mitochondria was observed, in ascorbate/iron treated synaptosomes. Idebenone (50 microM) prevented the increased formation of ROS in both synaptosomal compartments, vitamin E (150 microM) protected partially this formation in mitochondria, whereas reduced glutathione (250 microM) (GSH) was ineffective. After ascorbate/iron treatment an increase in lipid peroxidation occurred as compared to control, which was completely inhibited by idebenone. A decrease in protein-SH content was also observed, and it was prevented by Vitamin E, idebenone and GSH. When synaptosomes were treated with ascorbate/iron the levels of GSH decreased, and the levels of oxidized glutathione (GSSG) increased as compared to controls under these conditions. Glutathione peroxidase activity was unchanged, whereas an inhibition of glutathione reductase activity was observed. These data suggest that the increased formation of free radicals in synaptosomes leads to lipid and protein oxidation, the role of the endogenous GSH being essential to protect protein thiol-groups against oxidative damage in order to maintain enzyme activity.

Topics: Adenine Nucleotides; Animals; Antioxidants; Ascorbic Acid; Benzoquinones; Brain; Free Radical Scavengers; Free Radicals; Glutathione; Iron; Lipid Peroxidation; Male; Nerve Tissue Proteins; Oxidation-Reduction; Oxidative Stress; Rats; Rats, Wistar; Reactive Oxygen Species; Sulfhydryl Compounds; Synaptosomes; Ubiquinone; Vitamin E

Rats were given vitamin E (Vit-E), idebenone (ID), or vitamin C (Vit-C) in their food for 2 or 4 weeks. After feeding, the ability of rats to reduce 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol) in terms of the half-life of Tempol was examined as a specific marker. Tempol was repeatedly injected intravenously, and its half-life was serially evaluated by an in vivo electron spin resonance (ESR) technique. The radical-reducing ability in rats was enhanced differently by Vit-E, ID, and Vit-C, i.e., slow onset of the ability after Vit-E and ID (lipid-soluble antioxidants) and fast onset after Vit-C (a water-soluble antioxidant).

Topics: Animals; Antioxidants; Ascorbic Acid; Benzoquinones; Cyclic N-Oxides; Electron Spin Resonance Spectroscopy; Male; Oxidation-Reduction; Rats; Rats, Wistar; Spin Labels; Ubiquinone; Vitamin E