Raxofelast, a hydrophilic vitamin E-like antioxidant, stimulates wound healing in genetically diabetic mice

Background. Impaired wound healing is a well-documented phenomenon in exper imental and clinical diabetes. Emerging evidence favors the involvement of free radicals in the pathogenesis of diabetes-related healing deficit. This study assessed the effect of systemic administration of raxofelast, a prot ective membrane antioxidant agent, on wound healing by using healing-impair ed (db/db) mice. Methods. The wound healing effect of raxofelast was investigated by using a n incisional skin-wound model produced on the back of female diabetic C57BL /KsJ db+/db+ mice and their healthy littermates (db+/+m). Animals were then randomized to the following treatment: raxofelast (15 mg/kg/d intraperiton eally) or ifs vehicle (dimethyl sulfoxide/sodium chloride 0.9%, 1:1, vol/vo l). The animals were killed on different days, and the wounded skin tissues were used for histologic evaluation and for analysis of malondialdehyde (M DA) level and myeloperoxide (MPO) activity, wound breaking strength, and co llagen content. Results. Diabetic mice showed delayed wound healing together with low colla gen content, breaking strength, and increased MDA levels and MPO activity w hen compared with their healthy littermates. The administration of raxofela st did not modify the process of wound repair in healthy (db/+) mice, but s ignificantly improved impaired wound healing in diabetic mice through the s timulation of angiogenesis, reepithelialization, synthesis, and maturation of extracellular matrix. Furthermore, raxofelast treatment significantly re duced MDA levels, MPO activity, and increased the breaking strength and col lagen content of the wound. Conclusions. The current study Provides evidence that raxofelast restores w ound healing to nearly normal levels in experimental diabetes-impaired woun ds and suggests that an increased lipid peroxidation in diabetic mice may h ave a role in determining a defect of wound repair.