Effect of topical magnesium application on epidermal integrity and barrier function

Abstract

Dead Sea therapy is one of the oldest forms of treatment for skin disease and some chronic inflammatory diseases like arthritis and psoriasis. Much of the research to date has attributed the clinical effects of Dead Sea therapy to its mineral composition; mostly to magnesium salts.Magnesium salts, such as magnesium sulphate (Epsom salts), have long been used as a spa product and as a therapeutic to manage clinical conditions. The rationale of this PhD research was to understand the role of topically applied magnesium ions in epidermal integrity of human skin. We compartmentalized this research project into studying physiological, metabolic and proteolytic changes occurring at different layers of the skin. To begin with, we investigated the permeability of magnesium ions through stratum corneum. In Chapter 3, we developed a method to stain skin sections using mag-fura-2, a fluorescent dye that specifically binds to magnesium ions. When magnesium chloride (MgCl 2 ) solution was topically applied on normal and tape stripped skin, we observed that it is possible for magnesium ions to permeate through stratum corneum. We also varied the concentration and time of exposure of MgCl 2 solutions and found that at higher magnesium concentration, permeability is faster and penetration increases with progression of time.To further characterize permeability of the skin to magnesium, we blocked individual hair follicles using a novel method and subsequently treated skin with MgCl 2 solution. We found that hair follicles significantly contribute towards the permeation of magnesium ions. In Chapter 4, the hypothesis tested was that magnesium accelerates barrier recovery. Experiments were conducted on volunteers who did not have any history of skin conditions. We caused stratum corneum disruption on their volar forearm through tape stripping and subsequently treated that defined region with different salt solutions. The parameters we considered for understanding barrier function were transepidermal water loss, skin hydration and skin pH over 96 hours with repeated treatment at 24-hour intervals. We found that treatment with a variety of salt solutions, including magnesium chloride did not aid in lowering the TEWL to levels pre-tape stripping and no changes to skin pH were observed. However, we observed that treating the skin with 1.9 M magnesium solution nearly 2 fold (p < 0.05) increased hydration at 6 hours, relative to baseline at time zero, whereas water treatment increased hydration only 1.2 fold, and the hydration returned to normal levels within 24 hours in both cases. Skin barrier formation is a continuous process and occurs as a result of differentiating epidermal cells subsequently leading to terminal differentiation. In the case of disrupted barrier, the epidermal cells differentiate to replenish the lost layers of stratum corneum.Therefore as an extension to Chapter 4, experiments in Chapter 5 involved understanding the metabolic changes occurring in all three layers of the epidermis -granulosum, spinosum, bas...