Hyperbaric oxygen (HBO) therapy is proven to be very successful for diabetic foot ulcer (DFU) treatment and has been demonstrated to have antimicrobial effect, increased angiogenesis and enhanced collagen synthesis. In the present study, we investigated the molecular mechanism underlying HBO therapy particularly the role of Nrf2 in wound healing process. In addition, we have studied the levels of angiogenic markers in ulcer tissues and their correlation with Nrf2 during HBO therapy compared with a standard therapy (Non-HBO) for DFU. A total of 32 patients (16 males and 16 females) were recruited and randomized to standard wound care alone (n=17) or HBO therapy in combination with standard wound care (n=15). Our results showed that the tissue levels of Nrf2 along with the downstream targets showed significant increase in patients who underwent HBO therapy. It induces angiogenesis with significantly increasing the levels of angiogenesis markers such as EGF, VEGF, PDGF, FGF-2 and CXCL10 in the tissue samples. The HIF-1α expression showed a 4.9-fold and eNOS with a 4.5-fold among HBO therapy when compared to Day 0 subjects. HBO therapy sensitize macrophages to release FGF-2 and EGF thereby promotes angiogenesis. Further it increased the levels of CXCL-8, which is a potent neutrophil attractant thereby promote the release chemokine CCL2, a well-known mediator of neovascularization. The Spearman’s correlation showed that Nrf2 have a positive correlation with EGF, VEGF, PDGF and HIF-1α.

In conclusion, the findings of the present study suggest that HBO therapy promote wound healing by increasing oxygen dispersion to damaged tissues, stimulating angiogenesis, alleviating inflammation, and increasing the levels of NO. It is evidenced that elevated Nrf2 transiently regulates angiogenic gene expression in wound biopsies, which may enhance chronic wound healing.


D. Umapathy: None. P. Vikraman: None. V. Alladi: None. S. Arumugam: None. S. Dornadula: None. K. Amin: None. R. Kesavan: None. R. Kunka Mohanran: None.

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