Sottili Mariangela, Mangoni Monica, Gerini Chiara, Salvatore Giulia, Castiglione Francesca, Desideri Isacco, Bonomo Pierluigi, Meattini Icro, Greto Daniela, Loi Mauro, Francolini Giulio, Perna Marco, Grassi Roberta, Biti Giampaolo, Livi Lorenzo
Radiotherapy Unit, Department of Biomedical, Experimental and Clinical Sciences "Mario Serio", University of Florence, Firenze, Italy.
Department of Clinical and Experimental Medicine, University of Florence, Firenze, Italy.
Head Neck. 2018 Mar;40(3):577-583. doi: 10.1002/hed.25017. Epub 2017 Nov 20.
Oral mucositis is a side effect of treatment regimens containing 5-fluorouracil (5-FU). The purpose of this study was to present our evaluation to see if rosiglitazone (RGZ) protected normal tissues from chemotherapy-induced oral mucositis.
C57BL/6J mice were treated with 5-FU for 5 days, with or without RGZ. Mice were euthanized after 5, 8, 11, or 15 days, and mucosal segments were collected.
The RGZ did not affect the 5-FU-induced decrease in mouse body weight. The 5-FU caused loss of epithelial architecture, collagen fiber impairment, and inflammatory infiltration. The RGZ reduced leukocyte infiltration, preserved tissue structure, and dampened the 5-FU-induced expression of p53 and matrix metalloproteinase (Mmp)-2 after 5 days, and of Mmp-2 and interleukin (Il-1β after 15 days. The RGZ inhibited the 5-FU-induced increase of transforming growth factor-beta (TGF-β) and nuclear factor-kappa B (NF-κB) proteins and restored collagen protein levels.
The RGZ had a protective effect on oral mucosa damaged by chemotherapy. These data encourage the further study of RGZ for the prevention of 5-FU-induced mucositis in patients with cancer.
口腔黏膜炎是含5-氟尿嘧啶（5-FU）治疗方案的一种副作用。本研究的目的是展示我们的评估结果，以确定罗格列酮（RGZ）是否能保护正常组织免受化疗诱导的口腔黏膜炎影响。
C57BL/6J小鼠接受5天的5-FU治疗，同时或不同时给予RGZ。在第5、8、11或15天后对小鼠实施安乐死，并收集黏膜段。
RGZ不影响5-FU诱导的小鼠体重下降。5-FU导致上皮结构丧失、胶原纤维受损和炎症浸润。RGZ减少了白细胞浸润，保留了组织结构，并在5天后抑制了5-FU诱导的p53和基质金属蛋白酶（Mmp）-2的表达，在15天后抑制了Mmp-2和白细胞介素（Il）-1β的表达。RGZ抑制了5-FU诱导的转化生长因子-β（TGF-β）和核因子-κB（NF-κB）蛋白增加，并恢复了胶原蛋白水平。
RGZ对化疗损伤的口腔黏膜有保护作用。这些数据鼓励进一步研究RGZ用于预防癌症患者5-FU诱导的黏膜炎。
