Photodegraded nifedipine stimulates uptake and retention of iron in human epidermal keratinocytes

Abstract

Photodegraded nifedipine has been shown to increase uptake of nontransferrin bound iron into erythroid cells. If iron could be loaded into keratinocytes, it might be possible to exploit epidermal desquamation for the purpose of eliminating potentially toxic amounts of iron from the body. We investigated the ability of photodegraded nifedipine to stimulate iron transport and accumulation in human epidermal keratinocytes. Nifedipine was degraded to its nitroso derivative by exposure to sunlight. 59Fe uptake was measured in keratinocyte monolayers, and total iron content was measured in stratified epidermal cultures. Photodegraded nifedipine increased iron uptake into keratinocytes 80-fold compared to controls. The effect of photodegraded nifedipine on iron uptake was rapid, was concentration dependent and occurred at physiologically relevant concentrations of nonprotein-bound iron. Stimulation of iron uptake by photodegraded nifedipine was independent of transferrin and worked equally well in the presence or absence of serum proteins. Iron content in keratinocytes was increased 3-fold by four daily treatments with photodegraded nifedipine. The increased iron content resulting from photodegraded nifedipine treatment was retained during a 4 d Washout period. Photodegraded nifedipine may be a way delivering clinically significant amounts of iron to the epidermis.