Ferrous Ferric Chloride Stimulates the Proliferation of Human Skin Keratinocytes, Melanocytes, and Fibroblasts in Culture

Abstract

Ferrous ferric chloride (FFC®) is a distinct form of aqueous iron made up of a complex of ferrous chloride and ferric chloride that participates in both oxidation and reduction reactions. Although FFC is known to stimulate cellular function, its precise mechanism of action is largely unknown. My previous study showed that FFC stimulated the proliferation of cultured epidermal keratinocytes and melanocytes derived from newborn mice, suggesting that FFC stimulates their function of mice. However, it is not known whether FFC stimulates the proliferation of keratinocytes and melanocytes derived from human skin. Moreover, it is unknown whether FFC stimulates the proliferation of human skin fibroblasts. Pairogen® (Akatsuka Co., Tsu, Japan) is a drink comprising FFC, vinegars, and vitamins, Pairogen Gold® (Akatsuka) contains herbal medicines in addition to FFC, vinegars, and vitamins, while Noncalorie Pairogen® (Akatsuka) contains low molecular weight collagen and hyaluronic acid in addition to FFC, vinegars and vitamins. To clarify whether FFC in addition to the natural factors included in these drinks stimulates the proliferation of human skin cells, FFC and these different drinks were added to culture media and tested for their proliferation-stimulating activity on skin cells. FFC, Pairogen, and Pairogen Gold equally doubled the growth rate of cultured human keratinocytes, melanocytes, and fibroblasts. Non-calorie Pairogen tripled the growth rate of human fibroblasts, but Non-calorie Pairogen only doubled the growth rate of human keratinocytes and melanocytes. FFC plus low molecular weight collagen tripled the growth rate of human fibroblasts, whereas FFC plus low molecular weight hyaluronic acid only doubled the growth rate of human fibroblasts. Low molecular weight collagen, with or without hyaluronic acid failed to stimulate the proliferation of fibroblasts. These results suggest that FFC stimulates the proliferation of human skin keratinocytes and melanocytes. Moreover, FFC markedly stimulates the proliferation of human skin fibroblasts synergistically with low molecular weight collagen.