Enhanced Cosmetic Results in African American Skin Pigmentation Using a Polymer Hydrogel with Oxygen Free Radical Binding Capacity
Kim Eldridge, RN, James Gleaves, MD, Jeffrey Niezgoda, MD and Richard M. Millis, PhD
Rush Hospital Wound Care, Hyperbaric and Limb Salvage Center, Meridian MS 39301
St Luke’s Center for Comprehensive Wound Care and Hyperbaric Oxygen Therapy, Milwaukee, WI 53215
Department of Physiology & Biophysics, Howard University College of Medicine, Washington, DC 20059
We observed marked improvement in the skin pigmentation of patients possessing cutaneous wounds that were treated with a tetramethyl piperidine oxygen free radical scavenging agent. These findings are consistent with research demonstrating correlations between antioxidant and tyronsinase mediated melanin producing activity in human skin epithelial cells. We conclude that the tetramethyl piperidine treatment may limit the hypopigmentation commonly associated with cutaneous wound healing by mechanisms akin to the effects of catalase and superoxide dismutase.
Irregular skin pigmentation in dark skinned people, such as African Americans, may be caused by a variety of mechanisms, including changes in production of melanin by skin melanocytes (1), production of nitric oxide by endothelial cells lining blood vessel walls (2) and microbial (1) or fungal growth (3). Exposure to the sun’s ultraviolet radiation (4, 148) and hormonal and genetic factors (4) modulate the expression of melanin and, therefore, skin pigmentation. Pigmentation is determined by the amount of melanin, the location of the melanin and melanocytes, the balance between oxygenated and reduced hemoglobin, and the presence of vitamins and other external pigments (1). Melanin protects skin from ultraviolet radiation and retards aging; indeed, dark skinned individuals are thought to look younger than lighter ones. When treating cutaneous wounds in darkly pigmented individuals, hypopigmentation can be a significant challenge to wound care clinicians. Poor healing is characterized by excessive inflammation (5-7), cicatrices (scars) (8, 9) and abnormal pigmentation (10) In this report, we describe a series of patients shown to have markedly better cosmetic results characterized by more rapid return of normal skin pigmentation when the therapeutic regimen included a hydroxyethyl methacrylate hydrophilic gel polymer with a tetramethyl piperidine for oxygen free radical binding compared to when using similar treatments not possessing the hydrogel with oxygen free radical scavenging capacity. Our findings suggest that cutaneous wound treatments using tetramethyl piperidines for oxygen free radical scavenging may decrease the physically and psychologically devastating effects of skin hypopigmentation associated with wound healing.
Three enzymes are necessary to initiate and maintain pigmentation (melanogenesis) and darken human skin. Tyrosinase, the key enzyme for melanogenesis, catalyzes oxidation of phenols (catechols) to quinone products such as benzoquinone (11). Hydroxyquinones are potent skin whitening agents because of their structural similarity to benzoquinone and, hence, their capacity to inhibit tyrosinase activity by end-product inhibition (12). Activity of tyrosinase is closely associated with the activities of phenylalanine hydroxylase (PAH) and tyrosine hydroxylase (TH). L-phenylalanine uptake and turnover is regulated by the activity of PAH which converts L-phenylalanine to L-tyrosine and provides the substrate for both TH and tyrosinase activity (13). At low pH, TH produces L-DOPA which also activates the tyrosinase in melanocytes and, by a series of intermediate reaction, produces dopaquinone, quinone and melanins as the end-products of this pathway (14). Oxidative stress is associated with redox reactions which are known to lower the pH and increase the hydrogen peroxide concentration of cells which may, therefore, contribute to hyperpigmentation in skin exposed to UV radiation by activating TH and tyrosinase which, in turn, produces L-DOPA, dopaquinone, quinone and melanins (15). In darkly pigmented skin, melanin producing cells (melanocytes) appear to employ two protective strategies; one represented by the activity of tyrosinase which, as previously described, promotes melanogenesis. Another melanocyte protection is based on the activity of catalase (16) which scavenges reactive oxygen species (ROS), the main indicators of oxidative stress. Lightly pigmented melanocytes possess low levels of tyrosinase and catalase activities and are, therefore, more susceptible than darkly pigmented melanocytes to UV damage because of a relative lack of melanin producing and ROS scavenging (antioxidant) capacity (16). The results of the present study demonstrate maintenance of pigmentation and marked protection from hypopigmentation associated with wound healing in the presence of an antioxidant, ROS scavenging treatment in African-Americans with darkly pigmented skin. The proanthocyanidins from grape seeds, as well as a number of other chemicals with antioxidant activity, protect skin cells from UV induced damage and hyperpigmentation (17). Based on the results of UV exposures, it seems paradoxical that our tetramethyl piperidine treatment, which scavenges ROS, would help maintain pigmentation and protect skin from hypopigmentation. However, studies have demonstrated the capacity for ROS to inhibit a wide variety of enzymes, such as tyrosinase, the key enzyme of melanogenesis (18). The inflammatory phase of wound healing is associated with an “oxidative burst” in metabolism which often produces an excessive amount of ROS (19). Hence, the tetramethyl piperidine treatment, described in this report, may protect skin tissues, especially those containing cells with an inadequate amount of antioxidants, from hypopigmentation by maintaining tyrosinase activity and melanogenesis via a mechanism which mimics the ROS scavenging activity of catalase and superoxide dismutase.
In summary, we observed marked improvement in the skin pigmentation of patients possessing cutaneous wounds that were treated with a tetramethyl piperidine oxygen free radical scavenging agent. These findings are consistent with research demonstrating correlations between catalase and superoxide dismutase antioxidant and tyronsinase melanin synthesizing activities in human skin epithelial cells. We conclude that tetramethyl piperidine treatments may limit the hypopigmentation commonly associated with cutaneous wound healing by mechanisms akin to the effects of catalase and superoxide dismutase.
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