Experimental observations in the rat on the influence of cadmium on skin wound repair

Wound healing in the skin depends upon the availability of appropriate trace metals as enzyme cofactors and structural components in tissue repair. The present study forms part of a series of experimental investigations to examine the influence of xenobiotic elements with no known nutritional function and which are known to compete with essential trace metals. It was designed to investigate further the importance of trace metals in wound healing as an aid to wound management and to identify mechanisms of nonhealing which constitute a major problem in human medicine. Surgically induced skin wounds in young adult male Wistar rats were exposed topically to 0.2 ml of 0.01, 0.10 or 1.0% cadmium chloride (aq.) daily for up to 10 days. Control wounds received de-ionized water only. Wounds exposed to cadmium chloride at 0.01 or 0.10% healed in a similar fashion to controls and exhibited a comparable histological profile with metallothionein distribution. Wounds receiving 1.0% cadmium chloride failed to heal or fully re-epithelialize within 7 days and animals were humanely killed. They showed a persistent mass of inflammatory cell infiltration, oedema, wound debris and aberrant epidermal cell growth. Metallothionein concentrations in the epidermis and fibroblasts of the papillary dermis increased greatly by 5 days postwounding and remained high through the observation period. Cadmium was identified in the liver, kidney and wound sites. In the wound, 1.0% cadmium chloride induced statistically significant (P > 0.001) changes in local concentrations of zinc and calcium at key stages in the healing process, and as a consequence disturbed the trace metal balance necessary for normal wound repair. Zinc levels were increased twofold after 7 days, but calcium was markedly reduced. Local changes in the distribution of metallothionein indicate interaction of cadmium and trace metal carrier proteins as a probable mechanism for impaired wound healing. The cytotoxicity of cadmium is considered to be largely responsible.