Novel mitochondria-targeted antioxidants, “Skulachev-Ion” derivatives, accelerate dermal wound healing in animals

Abstract

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.

Effect of astaxanthin on cutaneous wound healing

“…While the production of ROS in the early phase is significantly higher than normal in order to defend against invading microorganisms and transmit intercellular signals supporting the process of inflammation,11,12 astaxanthin may be quenching and scavenging excessive ROS and RNS, which is consistent with our result which showed significantly decreased expression of iNOS, an oxidative stress marker, in the astaxanthin-treated group. As a result, activation of the NF-kB pathway may be prevented, leading to reduced pro-inflammatory gene transcription and pro-inflammatory cytokine production 13,14. Second, astaxanthin may have an inhibitory effect on the expression of adhesion molecules.…”

Role of mitochondrial reactive oxygen species in age-related inflammatory activation of endothelium

“…In the current study, we used SkQ1 antioxidant, based on the plastoquinone moiety linked to dodecyltriphenylphosphonium cation that targets SkQ1 to mitochondria [26]. SkQ1 and its analogs are efficient in the prevention of some age-associated pathologies, and they have therapeutic effects in animal models of diseases associated with inflammatory response (heart, brain, and kidney ischemic injury [27, 28], pyelonephritis [29], eye diseases [30, 31], sarcopenia [32], and dermal wound healing [33]). SkQ1 delays the development of various markers of aging and prolongs the lifespan of various animals [20, 22, 34, 35].…”

Specific inhibition of mitochondrial oxidative stress suppresses inflammation and improves cardiac function in a rat pneumonia-related sepsis model

“…Because mitochondria are the main organelles that produce reactive oxygen species (ROS), more effective therapeutic benefits may be achieved by concentrating antioxidant activities specifically in mitochondria. Recently, strategies for mitochondria-targeted delivery of antioxidants have been developed (2,4,22,70). One such approach covalently links biomolecules to lipophilic triphenylphosphonium cation (TPP ϩ ).…”