RESUMEN
The imbalance in oxidant production and chronic inflammation are the main mechanisms that lead to the detrimental effects of diabetes on skin wound healing. Thus, administration of antioxidants could improve diabetic wound healing. This study aimed to understand the effects of extra virgin olive oil (EVOO) or hydroxytyrosol (HT) in skin wound healing under diabetic conditions. Skin wounds in streptozotocin-induced diabetic mice were topically treated with HT. Some diabetic animals were fed with a diet rich in EVOO. Wounds were harvested 7 days later. In in vitro assays, fibroblasts and macrophages were treated with high levels of glucose and HT. The EVOO or HT promoted wound closure and collagen deposition in diabetic mouse wounds. The EVOO or HT reduced the number of infiltrated neutrophils, tumour necrosis factor-α, lipid peroxidation, and nuclear factor erythroid 2-related factor 2 in diabetic mouse wounds. The EVOO or HT also increased the number of macrophages with anti-inflammatory phenotype and interleukin-10 in diabetic mouse wounds. In the in vitro assays, HT promoted the fibroblast migration, collagen gel contraction, and switched macrophages to an anti-inflammatory phenotype under high glucose conditions. In conclusion, the diet supplementation with EVOO or topical application of HT promotes skin wound healing under diabetic conditions and can be a possible therapeutic tool for the treatment of those lesions.
RESUMEN
Hydroxytyrosol (HT) or dimethyl fumarate (DMF), activators of nuclear factor erythroid 2-related factor 2 (Nrf2), may reduce obesity in high-fat diet (HFD)-fed animals; nevertheless, the role of these activators on skin tissue repair of HFD-fed animals was not reported. This study investigated whether HT or DMF could improve skin wound healing of HFD-fed obese animals. Mice were fed with an HFD, treated with HT or DMF, and full-thickness skin wounds were created. Macrophages isolated from control and obese animals were treated in vitro with HT. DMF, but not HT, reduced the body weight of HFD-fed mice. Collagen deposition and wound closure were improved by HT or DMF in HFD-fed animals. HT or DMF increased anti-inflammatory macrophage phenotype and protein Nrf2 levels in wounds of HFD-fed mice. Lipid peroxidation and protein tumor necrosis factor-α levels were reduced by HT or DMF in wounds of HFD-fed animals. In in vitro, HT stimulated Nrf2 activation in mouse macrophages isolated from obese animals. In conclusion, HT or DMF improves skin wound healing of HFD-fed mice by reducing oxidative damage and inflammatory response. HT or DMF may be used as a therapeutic strategy to improve the skin healing process in individuals with obesity.