Deferiprone Stimulates Aged Dermal Fibroblasts Via HIF-1α Modulation

BACKGROUND: The transcription factor Hypoxia Inducible Factor 1 alpha (HIF-1α) is responsible for tissue homeostasis and regeneration and presents reduced functionality in advanced age. In addition to absence of oxygen, sequestration of iron also stimulates HIF-1α. Therefore, we analyzed the efficacy of the iron-chelator Deferiprone to stimulate dermal fibroblasts. OBJECTIVES: Our main objective is to quantify the Deferiprone concentrations able to stimulate dermal fibroblasts in-vitro and to correlate the effective DFP concentrations with its ability to penetrate the epidermis, reach the dermis and activate HIF-1α in-vivo. METHODS: We measured cell proliferation, the metabolic activity, HIF-1α expression and Lactatdehydrogenase levels of both young and aged fibroblasts after a 24h in-vitro preconditioning with Deferiprone. Moreover, we evaluated cell survival rates and morphology with different cellular stainings. Finally, we performed a transdermal permeation study with a 1% Deferiprone topical formulation to quantify the concentration able to reach the dermis. RESULTS: In vitro administration of iron-chelation therapy (DFP 312.5 µg/ml - 156 µg/ml) on aged fibroblasts resulted in an activation of different anti-aging processes. The concentration able to reach the dermis after 24h was 1.5% (0.15 mg/ml), which corresponds well with the effective doses of our laboratory analyses. CONCLUSION: The activation of HIF-1α via DFP enhances cell metabolism, proliferation and survival of fibroblasts while reducing LDH levels. Modulation of HIF-1α is linked to activation of key regeneration enzymes and proteins, and by proxy, anti-aging. Therefore, the anti-aging properties of DFP and its satisfactory dermal penetration make it a promising regenerative agent.     «

BACKGROUND: The transcription factor Hypoxia Inducible Factor 1 alpha (HIF-1α) is responsible for tissue homeostasis and regeneration and presents reduced functionality in advanced age. In addition to absence of oxygen, sequestration of iron also stimulates HIF-1α. Therefore, we analyzed the efficacy of the iron-chelator Deferiprone to stimulate dermal fibroblasts. OBJECTIVES: Our main objective is to quantify the Deferiprone concentrations able to stimulate dermal fibroblasts in-vitro and to co...     »