Histology and Embryology Department, State University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
Laboratory of Histocompatibility and Cryopreservation, State University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
J Biochem Mol Toxicol. 2024 Feb;38(2):e23652. doi: 10.1002/jbt.23652.
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.
羟基酪醇（HT）或富马酸二甲酯（DMF），可激活核因子红细胞 2 相关因子 2（Nrf2），可能会减少高脂肪饮食（HFD）喂养动物的肥胖；然而，这些激活剂对 HFD 喂养动物皮肤组织修复的作用尚未报道。本研究旨在探讨 HT 或 DMF 是否可以改善 HFD 喂养肥胖动物的皮肤伤口愈合。将小鼠用 HFD 喂养，用 HT 或 DMF 处理，并在其背部造成全层皮肤伤口。将来自对照和肥胖动物的巨噬细胞在体外用 HT、DMF 处理。DMF，但不是 HT，可降低 HFD 喂养小鼠的体重。HT 或 DMF 可改善 HFD 喂养动物的胶原沉积和伤口闭合。HT 或 DMF 可增加 HFD 喂养小鼠伤口中抗炎型巨噬细胞表型和蛋白 Nrf2 水平。HT 或 DMF 可降低 HFD 喂养动物伤口中的脂质过氧化和蛋白肿瘤坏死因子-α水平。在体外，HT 可刺激来自肥胖动物的巨噬细胞中的 Nrf2 激活。总之，HT 或 DMF 通过减少氧化损伤和炎症反应来改善 HFD 喂养小鼠的皮肤伤口愈合。HT 或 DMF 可作为一种治疗策略，改善肥胖个体的皮肤愈合过程。
