Effects of Hydrogen Peroxide on Different Models of Wound Healing

Abstract

It has been established that low concentrations of H₂O₂ are produced in wounds. Yet at the same time, there is evidence that excessive oxidative damage is correlated with chronic wounds. In this thesis we explored the effects of H₂O₂ in keratinocyte cell culture models and an <i>in vivo</i> excision wound model of wound healing.

H₂O₂ stimulates a persistent ERK phosphorylation in HaCaT keratinocytes which was found to be important in cell proliferation and migration. H₂O₂ also increases the production of proinflammatory and pro-angiogenic cytokines such as Vascular endothelial growth factor, Interleukin-8, Granulocyte-macrophage colony-stimulating factor, Tumor necrosis factor-a, interleukin-6 and Interferon gamma-induced protein 10, in HaCaT keratinocytes. H₂O₂ was found to increase re-epithelialization in a primary fibroblast-keratinocyte co-culture model as well.

In a C57BL/6 mice excision wound model, low concentrations of H₂O₂ (10 mM) were found to enhance angiogenesis while high concentrations of H₂O₂ (166 mM) retarded wound closure and connective tissue formation. High concentrations of H₂O₂ also increased the levels of MMP-8 in the wounds, which could be the cause of reduced connective tissue formation. Wounding was found to increase oxidative lipid damage, as measured by F₂-isoprostanes, but H₂O₂ treatment does not significantly increase it even at concentrations that delay wound healing. This challenges the putative claim that oxidative damage contributes to the pathology of poor healing wounds.