The role of iron in the skin and cutaneous wound healing

Abstract

In this review article we discuss current knowledge about iron in the skin and the cutaneous wound healing process. Iron plays a key role in both oxidative stress and photo-induced skin damage. The main causes of oxidative stress in the skin include reactive oxygen species (ROS) generated in the skin by ultraviolet (UVA) 320–400 nm portion of the UVA spectrum and biologically available iron. We also discuss the relationships between iron deficiency, anemia and cutaneous wound healing. Studies looking at this fall into two distinct groups. Early studies investigated the effect of anemia on wound healing using a variety of experimental methodology to establish anemia or iron deficiency and focused on wound-strength rather than effect on macroscopic healing or re-epithelialization. More recent animal studies have investigated novel treatments aimed at correcting the effects of systemic iron deficiency and localized iron overload. Iron overload is associated with local cutaneous iron deposition, which has numerous deleterious effects in chronic venous disease and hereditary hemochromatosis. Iron plays a key role in chronic ulceration and conditions such as rheumatoid arthritis (RA) and Lupus Erythematosus are associated with both anemia of chronic disease and dysregulation of local cutaneous iron hemostasis. Iron is a potential therapeutic target in the skin by application of topical iron chelators and novel pharmacological agents, and in delayed cutaneous wound healing by treatment of iron deficiency or underlying systemic inflammation.

Natural history and clinical outcome of junctional epidermolysis bullosa generalized intermediate due to a LAMA3 mutation

“…Deficient nutrition and chronic inflammation probably aggravate the compromised wound healing, while chronic wounds contribute to iron depletion . Our report highlights the importance of closely monitored, interdisciplinary care of these patients.…”

Use of Placental Membranes for the Treatment of Chronic Diabetic Foot Ulcers

“…Iron also plays a role in the activation of matrix metalloproteinases (MMPs), which is important for ECM remodeling. 19 Copper is essential for the activation of lysyl oxidase, cytochrome-C oxidase, and superoxide dismutase, enzymes that are critical for biogenesis of connective tissues, mitochondrial electron chain transfer, and antioxidant defense, respectively. Copper deficiency impairs the formation of collagen fibrils by inhibition of tropocollagen cross-linking performed by lysyl oxidase.…”

The Frequency of Iron Deficiency among Patients with Hemophilia

“…Haemophilic joint accumulates iron much more and longer than normal population, excess tissue iron is thought to play a role in synovitis and excess angiogenesis [15]. These newly formed vessels are more vulnerable to bleed.Iron impairs wound healing through number of mechanisms which include dysregulation of hypoxia-inducible factor expression, decreased lactoferrin mediated cell proliferation and alteration of collagen synthesis [16] In addition, iron deficiency has been shown to significantly impair immune response [17] and is associated with adverse cognitive and psychological effects which can lead to attention deficit, social withdrawal and poor intellectual attainment [18] Iron studies has not been adequately studied in haemophilia patients. In developing countries where due to poor sanitary conditions there is high incidence of intestinal infestation, occult blood loss through gastrointestinal tract could also be an important contributing factor to iron deficiency.…”