The Mechanisms of the Anti-Inflammatory and Anti-Apoptotic Effects of Omega-3 Polyunsaturated Fatty Acids during Methotrexate-Induced Intestinal Damage in Cell Line and in a Rat Model

Background: The aim of this study was to examine the anti-inflammatory and anti-apoptotic patterns of omega-3 polyunsaturated fatty acids (n-3 PUFAs) during methotrexate (MTX) induced intestinal damage in cell culture and in a rat model. Methods: Non-treated and treated with MTX HT 29 and HCT116cells were exposed to increasing doses of n-3 PUFAs and cell viability was evaluated using PrestoBlue^® assay. Male Sprague-Dawley rats were divided into 4 experimental groups: Control rats, CONTR+n-3 PUFA rats that were treated with oral n-3 PUFA, MTX rats were treated with MTX given IP, and MTX+n-3 PUFA rats were treated with oral n-3 PUFA before and following injection of MTX. Intestinal mucosal parameters and mucosal inflammation, enterocyte proliferation and apoptosis, TNF-α in mucosal tissue and plasma (ELISA), NF-κB, COX-2, TNF-α, Fas, FasL, Fadd, Bid, Bax and Bcl-2gene and protein levels were determined 72 h following MTX injection. Results: Exposure of HT 29 and HCT116cells to n-3 PUFA attenuated inhibiting effects of MTX on cell viability. MTX-n-3 PUFA rats demonstrated a lower intestinal injury score and enhanced intestinal repair. A significant decrease in enterocyte apoptosis in MTX+n-3 PUFA rats was accompanied by decreased TNF-α, FAS, FasL, FADD and BID mRNA levels. Decreased NF-κB, COX-2 and TNF-α levels in mucosa was accompanied by a decreased number of IELs and macrophages. Conclusions: n-3 PUFAs inhibit NF-κB/COX-2 induced production of pro-inflammatory cytokines and inhibit cell apoptosis mainly by extrinsic pathway in rats with MTX-induced intestinal damage.     

Prophylaxis with GM-CSF mouthwashes does not reduce frequency and duration of severe oral mucositis in patients with solid tumors undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue: a double blind, randomized, placebo-controlled study.

BACKGROUND: The aim of this study was to evaluate the effectiveness of granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwashes in the prevention of severe mucositis induced by high doses of chemotherapy. PATIENTS AND METHODS: Ninety consecutive patients affected by solid tumors and undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue were randomized to receive placebo versus GM-CSF mouthwash 150 micro g/day. Patients were stratified on the basis of the conditioning treatment and the consequent different risk of severe oral mucositis. Treatment was administered from the day after the end of chemotherapy until the resolution of stomatitis and/or neutrophil recovery. RESULTS: The statistical analyses were intention-to-treat and involved all patients who entered the study. The severity of stomatitis was evaluated daily by the physicians according to National Cancer Institute Common Toxicity Criteria. Both study and control groups were compared with respect to the frequency [30% versus 36%, chi(2) exact test, not significant (NS)] and mean duration (4.8 +/- 4.7 versus 4.4 +/- 2.7 days, t-test, NS) of severe stomatitis (grade > or =3). Oral pain was evaluated daily by patients themselves by means of a 10 cm analog visual scale: the mean (+/- standard error of the mean) maximum mucositis scores were 4.8 +/- 3.5 versus 4.2 +/- 3.5 cm (t-test, NS). Furthermore, 15/46 patients in the study group (33%) and 19/44 patients in the control group experienced pain requiring opioids (chi(2) exact test, NS). CONCLUSION: We did not find any evidence to indicate that prophylaxis with GM-CSF mouthwash can help to reduce the severity of mucositis in the setting of the patients we studied.     

系统护理对头颈癌患者放疗所致口腔黏膜炎预防效果的Meta分析

【摘要】 目的 探究系统护理干预对头颈癌患者放射性口腔黏膜炎的预防效果。方法 计算机检索中国期刊全文数据库、中文科技期刊全文数据库、万方数字化期刊全文数据库与PubMed,并通过其他资源补充检索,检索时间均从建库~2017年12月4日。由2名评价员根据纳入与排除标准对文献筛选、资料提取和严格质量评价后,采用RevMan53软件进行Meta分析。结果 最终纳入7项随机对照试验,共计827名患者。Meta分析结果显示,系统护理组口腔黏膜炎的发生情况主要以Ⅰ、Ⅱ级为主,Ⅲ级较少,Ⅳ级全无;而常规护理组则以Ⅱ、Ⅲ级为主,Ⅰ、Ⅳ级较少,但均有发生。结论 系统护理干预后能使放射性口腔黏膜炎的严重程度减轻,预防重型放射性口腔黏膜炎的发生。     

核黄素防治放射性口腔黏膜炎的疗效观察

目的观察核黄素磷酸钠联合康复新液用于鼻咽癌放射性口腔黏膜炎的预防及治疗效果。方法选取我院经病理确诊的74例初诊放疗的鼻咽癌患者,随机分为试验组及对照组。试验组37例:核黄素磷酸钠联合康复新液。具体用药:核黄素磷酸钠注射液30 mg+生理盐水100 m L,放疗期间1次/d静点;康复新液,放疗期间3次/d,10 m L/次,于口中含服3~5 min后缓慢咽下。对照组:康复新液单药,用药剂量及用法与试验组相同。结果 74例均纳入分析,试验组患者Ⅱ级以上放射性口腔黏膜炎的发生率明显低于对照组(37.8%vs.67.6%,P=0.019);试验组患者主要为轻度疼痛(67.6%),而对照组以中度疼痛为主(56.8%),两组疼痛程度比较,差异有统计学意义(P=0.035)。本研究中未观察到重度药物相关不良反应,提示药物安全性良好。结论核黄素磷酸钠联合康复新液防治放射性口腔黏膜炎的效果确切、安全,值得临床推广。