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Novel Mitochondria-Targeted Antioxidants, “Skulachev-Ion” Derivatives, Accelerate Dermal Wound Healing in Animals

I. A. Demianenko1,3, T. V. Vasilieva1,3, L. V. Domnina2,3, V. B. Dugina2,3, M. V. Egorov3, O. Y. Ivanova2,3, O. P. Ilinskaya1,3, O. Y. Pletjushkina2,3, E. N. Popova2,3, I. Y. Sakharov4, A. V. Fedorov1,3, and B. V. Chernyak2,3*

1Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia

2Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia; fax: (495) 939-3181; E-mail: bchernyak@yahoo.com

3Institute of Mitoengineering, Lomonosov Moscow State University, 119991 Moscow, Russia

4Chemical Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia

* To whom correspondence should be addressed.

Received November 30, 2009
It is shown that the novel mitochondria-targeted antioxidant SkQ1, (10-(6′-plastoquinonyl) decyltriphenylphosphonium) stimulates healing of full-thickness dermal wounds in mice and rats. Treatment with nanomolar doses of SkQ1 in various formulations accelerated wound cleaning and suppressed neutrophil infiltration at the early (7 h) steps of inflammatory phase. SkQ1 stimulated formation of granulation tissue and increased the content of myofibroblasts in the beginning of regenerative phase of wound healing. Later this effect caused accumulation of collagen fibers. Local treatment with SkQ1 stimulated re-epithelization of the wound. Lifelong treatment of mice with SkQ1 supplemented with drinking water strongly stimulated skin wounds healing in old (28 months) animals. In an in vitro model of wound in human cell cultures, SkQ1 stimulated movement of epitheliocytes and fibroblasts into the “wound”. Myofibroblast differentiation of subcutaneous fibroblasts was stimulated by SkQ1. It is suggested that SkQ1 stimulates wound healing by suppression of the negative effects of oxidative stress in the wound and also by induction of differentiation. Restoration of regenerative processes in old animals is consistent with the “rejuvenation” effects of SkQ1, which prevents some gerontological diseases.
KEY WORDS: mitochondria-targeted antioxidants, SkQ1, myofibroblasts, inflammation, skin wounds

DOI: 10.1134/S000629791003003X