Oxidative stress is widely recognized as an important factor in the delayed wound healing in diabetes. However, the role of mitochondrial reactive oxygen species in this process is unknown. It was assumed that mitochondrial reactive oxygen species are involved in many wound-healing processes in both diabetic humans and animals. We have applied the mitochondria-targeted antioxidant 10-(6′-plastoquinonyl)decyltriphenylphosphonium (SkQ1) to explore the role of mitochondrial reactive oxygen species in the wound healing of genetically diabetic mice. Healing of full-thickness excisional dermal wounds in diabetic C57BL/KsJ-db−/db− mice was significantly enhanced after long-term (12 weeks) administration of SkQ1. SkQ1 accelerated wound closure and stimulated epithelization, granulation tissue formation, and vascularization. On the 7th day after wounding, SkQ1 treatment increased the number of α-smooth muscle actin-positive cells (myofibroblasts), reduced the number of neutrophils, and increased macrophage infiltration. SkQ1 lowered lipid peroxidation level but did not change the level of the circulatory IL-6 and TNF. SkQ1 pretreatment also stimulated cell migration in a scratch-wound assay in vitro under hyperglycemic condition. Thus, a mitochondria-targeted antioxidant normalized both inflammatory and regenerative phases of wound healing in diabetic mice. Our results pointed to nearly all the major steps of wound healing as the target of excessive mitochondrial reactive oxygen species production in type II diabetes.
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.
Simulations of human disease in laboratory animals have continuously accompanied the history of medical discoveries and have helped researchers obtain useful information in medicine. The separation of physiological processes into their constituent components through modeling is one of the important parts of any research. Wound healing is a complex process. Using of models (in vitro, in vivo - on animals and humans) allowed large-scale research in this area, which significantly improved the knowledge of the healing mechanisms of both acute and chronic skin wounds. In parallel with the knowledge gained, the development of new wound treatments continues and the understanding of how to improve their care for the best results continues. Although in vitro and animal models have a place in these studies, by far the best models are those that rely on volunteers and provide physiologically more accurate mechanisms of skin pathogenesis and healing.
A comparative study of two commercially available injectable implants based on microparticles of various biodegradable materials (calcium hydroxyapatite and cross-linked collagen) was carried out using a murine model of subcutaneous implantation. The developed experimental model showed that both implants effectively replace the volume of soft tissues. Implant resorption was accompanied by a moderate chronic inflammatory response. The implant based on calcium hydroxyapatite microparticles caused pronounced post-injection swelling at 1 day after administration and demonstrated a more pronounced migration from the injection point. For this implant, an earlier onset of the process of replacing microparticles with autologous collagen fibers, accompanying its biodegradation, was observed. The implant based on cross-linked collagen microparticles had a greater lifting effect at the injection site and retained a longer effect of skin augmentation lasting for 12 months.
The article provides an overview of modern literature on the morphological and functional features of adipose tis- sue, as an organ that performs endocrine and immune function. Obesity plays a leading role in the formation of insulin resistance and metabolic syndrome. An increase in the mass of visceral adipose tissue leads to the dysregulation of the secretion of adipocytokines, which have a direct or indirect effect on the implementation of the effects of insulin in peripheral tissues and glucose metabolism, systemic inflammation, endothelial dysfunction, atherogenic status, accel- erating the development and progression of cardiovascular diseases, type 2 diabetes mellitus and other pathological conditions preceding their occurrence.
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