Effects of the tumour necrosis factor-α inhibitors pentoxifylline and thalidomide in short-term experimental oral mucositis in hamsters
Effects of the tumour necrosis factor-α inhibitors pentoxifylline and thalidomide in short-term experimental oral mucositis in hamsters
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DOI：
10.1111/j.1600-0722.2005.00216.x
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发表时间：
2005-06-01
影响因子：
1.9
通讯作者：
Ribeiro, RA
中科院分区：
文献类型：
--
作者：
Lima, V;Brito, GAC;Ribeiro, RA
口腔粘膜炎是癌症治疗的常见副作用。目前尚无明确的预防或治疗方法。由于已显示戊氨酰茶碱（PTX）和沙利度胺（thalidomide，MTX）抑制细胞因子合成，我们研究了这些细胞因子抑制剂在实验性口腔粘膜炎模型中的作用。通过施用5-氟尿嘧啶（5-FU），然后对颊囊进行机械创伤，在金黄仓鼠中诱导口腔粘膜炎。在第4、5、10、12、14和16天，对5-FU诱导的病变进行肉眼和显微镜检查，记录充血、红斑、水肿、炎性细胞浸润、出血区域、溃疡和脓肿的存在和强度。每天给予生理盐水（对照）、PTX（5、15、45 mg kg（-1））或PTX（10、30、90 mg kg（-1）），并在第10天处死动物进行肉眼和组织学分析以及髓过氧化物酶（MPO）活性测定。每天对动物称重，并对外周血进行白细胞总数和分类计数。发现PTX和紫杉醇可降低口腔粘膜炎和MPO活性的宏观和组织学参数。紫杉醇和地塞米松也能逆转外周嗜中性粒细胞增多症，但只有紫杉醇能阻止体重减轻。结果表明PTX和紫杉醇的保护作用，提示肿瘤坏死因子-α（TNF-α）在仓鼠5-FU诱导的口腔粘膜炎的病理生理学中具有重要作用。
Oral mucositis is a frequent side-effect of cancer therapy. A definitive method of prophylaxis or treatment is not yet available. As pentoxifylline (PTX) and thalidomide (TLD) have been shown to inhibit cytokine synthesis, we studied the effects of these cytokine inhibitors in an experimental oral mucositis model. Oral mucositis was induced in Golden hamsters by the administration of 5-fluorouracil (5-FU) followed by mechanical trauma of the cheek pouch. On days 4, 5, 10, 12, 14 and 16, lesions induced by 5-FU were examined macroscopically and microscopically, and the presence and intensity of hyperemia, erythema, edema, inflammatory cell infiltration, hemorrhagic areas, ulcers and abscesses were recorded. Saline (control), PTX (5, 15, 45 mg kg(-1)) or TLD (10, 30, 90 mg kg(-1)) were administered daily and animals were killed on day 10 for macroscopic and histological analysis and assay of myeloperoxidase (MPO) activity. Animals were weighed daily, and total and differential leukocyte counts were performed on peripheral blood. PTX and TLD were found to reduce the macroscopic and histological parameters of oral mucositis and MPO activity. PTX and TLD also reversed peripheral neutrophilia, but only PTX prevented weight loss. The results indicate a protective effect of PTX and TLD, suggesting an important role for tumour necrosis factor-alpha (TNF-alpha) in the pathophysiology of 5-FU induced-oral mucositis in hamsters.