Fig. 9
From: Regulation of HMGB1 release protects chemoradiotherapy-associated mucositis
Protective effect of NecroX-7 against chemo- and radiotherapy-induced oral mucositis (OM). Chemo- or radiotherapy-induced OM is initiated by direct injury to basal layer epithelial cells. These cells experience DNA damage and increased reactive oxygen species (ROS) levels, leading to mitochondrial dysfunction. Increased ROS levels in mitochondria trigger translocation of high-mobility group box 1 (HMGB1) from the nucleus to the cytoplasm, followed by its secretion extracellularly. A high level of HMGB1 triggers production of pro-inflammatory cytokines and activates the nuclear factor-κB pathway, resulting in development of OM. Therefore, HMGB1 has potential as a target for treatment of OM. Because NecroX-7 administration reduces mitochondrial ROS levels and blocks HMGB1 secretion, little HMGB1 remains in the mucosal tissue. This reduced HMGB1 level promotes cell regeneration and repair, which ameliorates OM
