Birgit A. Neudecker

Idebenone: a new antioxidant - Part I. Relative assessment of oxidative stress protection capacity compared to commonly known antioxidants

Topical applications of skin care products containing antioxidants have become increasingly popular. Numerous studies have elucidated the biological effects of these substances. General antiaging effects, anti‐inflammatory properties, photoprotective properties, and prevention of ultraviolet (UV) immunosuppression have been documented. However, a standardized method to characterize and compare the properties and oxidative stress protection capacity of antioxidants was lacking. A multistep in vitro process utilizing a variety of biochemical and cell biological methods combined with in vivo studies was designed to compare the oxidative stress protective capacity of commonly used antioxidants. Data were presented for L‐ascorbic acid, dl‐alpha‐tocopherol, kinetin, dl‐alpha lipoic acid, ubiquinone, and idebenone. Methods included using UV‐induced radical trapping/scavenging capacity measured by photochemiluminescence, pro‐oxidative systems (LDL‐CuSO4, microsome‐NADPH/ADP/Fe3+) with measurement of primary and secondary oxidation products, UVB irradiation of human keratinocytes, and in vivo evaluation, using the human sunburn cell (SBC) assay. Correlation and trends between in vitro and in vivo results were established, and the standardized test protocol was used to quantify oxidative stress protection capacity of antioxidants. Summarizing and totaling the data equally weighted for each oxidative stress study, the overall oxidative protection capacity scores of 95, 80, 68, 55, 52, and 41 were obtained for idebenone, dl‐alpha tocopherol, kinetin, ubiquinone, L‐ascorbic acid, and dl‐alpha lipoic acid, respectively. The higher the score, the more effective the overall oxidative stress protection capacity of the antioxidant became. This multistep protocol may serve as a standard in investigating and comparing new putative antioxidants for topical use as well as a valuable tool to assess the anti‐inflammatory properties, photoprotective properties, and prevention of UV immunosuppression of topical antioxidants.

Clinical efficacy assessment in photodamaged skin of 0.5% and 1.0% idebenone

Idebenone is an antioxidant lower molecular weight analogue of coenzyme Q10. Previously, idebenone was shown to be a very effective antioxidant in its ability to protect against cell damage from oxidative stress in a variety of biochemical, cell biological, and in vivo methods, including its ability to suppress sunburn cell (SBC) formation in living skin. However, no clinical studies have been previously conducted to establish the efficacy of idebenone in a topical skincare formulation for the treatment of photodamaged skin. In this nonvehicle control study, 0.5% and 1.0% idebenone commercial formulations were evaluated in a clinical trial for topical safety and efficacy in photodamaged skin. Forty‐one female subjects, aged 30–65, with moderate photodamaged skin were randomized to use a blind labelled (either 0.5% or 1.0% idebenone in otherwise identical lotion bases) skincare preparation twice daily for six weeks. Blinded expert grader assessments for skin roughness/dryness, fine lines/wrinkles, and global improvement in photodamage were performed at baseline, three weeks and six weeks. Electrical conductance readings for skin surface hydration and 35 mm digital photography were made at baseline after six weeks. Punch biopsies were taken from randomly selected subjects, baseline and after six weeks, and stained for certain antibodies (interleukin IL‐6, interleukin IL‐1b, matrixmetalloproteinase MMP‐1, collagen I) using immunofluorescence microscopy. After six weeks’ use of the 1.0% idebenone formula, a 26% reduction in skin roughness/dryness was observed, a 37% increase in skin hydration, a 29% reduction in fine lines/wrinkles, and a 33% improvement in overall global assessment of photodamaged skin. For the 0.5% idebenone formulation, a 23% reduction in skin roughness/dryness was observed, a 37% increase in skin hydration, a 27% reduction in fine lines/wrinkles, and a 30% improvement in overall global assessment of photodamaged skin. The immunofluorescence staining revealed a decrease in IL‐1b, IL‐6, and MMP‐1 and an increase in collagen I for both concentrations.

Aberrant serum hyaluronan and hyaluronidase levels in scleroderma

Background  Scleroderma, or systemic sclerosis, is characterized by aberrations of extracellular matrix deposition. These changes parallel early stages of wound healing when increased deposition of hyaluronan (HA) and collagen occur. Both processes result ultimately in the formation of fibrotic scar tissue. Activities of HA synthase and hyaluronidase, the enzymes that synthesize and degrade HA, are critical in HA turnover. Both become elevated whenever increased matrix deposition occurs. HA deposition occurs early in wound healing, and increases are documented in the circulation of scleroderma patients. We postulated that elevated HA and hyaluronidase may both be indicators of early‐stage disease in scleroderma, in parallel with early changes observed in wound healing. In an attempt to reduce HA accumulation and the associated fibrosis in scleroderma tissues, topical and intravenous hyaluronidase administrations have been used in the past as treatment modalities, with occasional success. This also suggested that hyaluronidase enzyme activity is involved in the disease process. It is now recognized that the hyaluronidases constitute an enzyme family. The somatic hyaluronidase Hyal‐1 is the only activity present in human serum.

Scleromyxedema‐like lesions of patients in renal failure contain hyaluronan: a possible pathophysiological mechanism

Background:  Patients with renal failure have been identified recently, some on dialysis, others with renal transplants, who have scleromyxedema‐like skin changes. These lesions are characterized grossly by extensive thickening of skin, brawny pigmentation, papules, and subcutaneous nodules. Mucinous deposits are observed histologically that resemble those in scleromyxedema.

A rapid, accurate, and facile method to quantify the antioxidative capacity of topical formulations.

Background/aims: Various methodologies have been developed to quantify antioxidant activity. A simple, rapid and accurate method is demanded. This study examined the antioxidative status of a pH balanced vitamin E containing formulation versus its vehicle control utilizing a photochemiluminescence device.