Mitochondria-targeted antioxidant SkQ1 improves impaired dermal wound healing in old mice

Abstract

The process of skin wound healing is delayed or impaired in aging animals. To investigate the possible role of mitochondrial reactive oxygen species (mtROS) in cutaneous wound healing of aged mice, we have applied the mitochondria-targeted antioxidant SkQ1. The SkQ1 treatment resulted in accelerated resolution of the inflammatory phase, formation of granulation tissue, vascularization and epithelization of the wounds. The wounds of SkQ1-treated mice contained increased amount of myofibroblasts which produce extracellular matrix proteins and growth factors mediating granulation tissue formation. This effect resembled SkQ1-induced differentiation of fibroblasts to myofibroblast, observed earlier in vitro. The Transforming Growth Factor beta (TGFβ)produced by SkQ1-treated fibroblasts was found to stimulated motility of endothelial cells in vitro, an effect which may underlie pro-angiogenic action of SkQ1 in the wounds. In vitro experiments showed that SkQ1 prevented decomposition of VE-cadherin containing contacts and following increase in permeability of endothelial cells monolayer, induced by pro-inflammatory cytokine TNF. Prevention of excessive reaction of endothelium to the pro-inflammatory cytokine(s) might account for anti-inflammatory effect of SkQ1. Our findings point to an important role of mtROS in pathogenesis of age-related chronic wounds.

Mitochondria‐Targeted Antioxidant SkQ1 Improves Dermal Wound Healing in Genetically Diabetic Mice

“…SkQ1 also prevented TNF-induced decomposition of VE-cadherin-containing contacts, following an increase in the permeability of endothelial cell monolayer [12]. SkQ1 also inhibited apoptosis of endothelial cells induced by high doses of TNF [28].…”

Aged kidney: can we protect it? Autophagy, mitochondria and mechanisms of ischemic preconditioning

“…It seems attractive to develop a protocol that reduces its negative impact on proliferation. We cannot exclude that this side effect may be much stronger in the elderly, where proliferative and regenerative processes are retarded [63]. For example, it has been shown that in telomeraseknockout mice, the time necessary to recover renal function after I/R was longer than in agematched wild-type controls [64].…”

Biological approaches for hypertrophic scars

“…And fibroblast dysfunction is linked to the overproduction of free ROS . Application of antioxidant or drugs with antioxidant properties could relieve the microenvironment of chronic inflammation, accelerate wound healing and alleviate scar formation on wounds . Similarly, classical traditional medicine, arsenic trioxide, could effectively inhibit the formation of rabbit ear scars through the overexpression of antioxidant genes …”