Background: Zinc salts are widely used as food supplements and medicinal mineral supplementation. Zinc deficiency is associated with impaired skin conditions. The influence of zinc on skin functionality has been proven in clinical investigations. Objective: Within the following study comparative in vitro experiments were performed to study the influence of zinc sulfate (ZnSO4) and zinc histidine (Zn(His)2) on the physiology of cultured natural human keratinocytes. Method: Proliferation of natural human keratinocytes was quantitatively assessed by measurement of 5-bromo-2-deoxyuridine (BrdU) incorporation against an oligomeric procyanidin as positive control. Differentiation was determined by monitoring involucrin formation. Cell viability and cytotoxicity were assessed by dimethylthiazolyldiphenyltetrazolium bromide (MTT) testing and quantification of lactate dehydrogenase. Results: Neither keratin synthesis as a late marker of cell differentiation nor mitochondrial cell activity were influenced by either zinc compound. The synthesis of involucrin, an early marker of differentiation, was significantly increased by both zinc salts, ZnSO4 being the more potent stimulator. Both zinc salts significantly increased cell proliferation, with the histidine complex being more potent. Effects were in the range of the positive control. Necrotic cell toxicity decreased significantly when Zn(His)2 was added to the cells. Conclusion: Under in vitro conditions Zn(His)2 is a strong proliferation inductor of keratinocytes with a better tolerability and a lower induction of differentiation behavior than ZnSO4.

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