ИСТИНА

Mitochondria-targeted antioxidants are the powerful tools for studies on the role of mitochondrial reactive oxygen species (mtROS) in physiological processes. We have shown that mitochondria- targeted antioxidant SkQ1, (10-(6′-plastoquinonyl) decyltriphenylphosphonium) stimulated healing of full-thickness dermal wounds in old (28 months) mice and in db/db mice with type II diabetes. Prolonged treatment with SkQ1 (250 nmol/kg per day) accelerated inflammatory as well as regenerative phases of wound healing. SkQ1 stimulated transition from neutrophil infiltration to accumulation of macrophages, formation of granulation tissue containing myofibroblasts, vascularization, and reepithelization of the wound. In endothelial cell culture SkQ1 prevented disorganization of cytoskeleton and intercellular contacts as well as surface expression of the neutrophil adhesion molecule ICAM1 induced by hyperglycemia and pro-inflammatory cytokine TNFa. SkQ1 also inhibited apoptosis induced by high doses of TNFa. These effects indicated the key role of mtROS in inflammatory response of endothelium and could underlay the anti-inflammatory effect of SkQ1. In the in vitro wound model SkQ1 stimulated movement of subcutaneous human fibroblasts into the ‘wound’ and myofibroblast differentiation. The stimulation of movement depended on modulation of Rho/Rac signaling, wile the differentiation was mediated by activation of TGFb. Anti-inflammatory, vasculoprotective and pro-differentiation effects of mitochondria-targeted antioxidants make them promising candidates for regenerative medicine.