Soares Pedro M G, Lopes Lorena O, Mota José Maurício S C, Belarmino-Filho José Nelson, Ribeiro Ronaldo A, Souza Marcellus Henrique L P de
Centro de Biomedicina, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE, Brasil.
Arq Gastroenterol. 2011 Jan-Mar;48(1):80-5. doi: 10.1590/s0004-28032011000100016.
Methotrexate and other anticancer agents can induce intestinal mucositis, which is one of the most common limiting factor that prevent further dose escalation of the methotrexate.
To evaluate the gastric emptying and gastrointestinal transit of liquids in methotrexate-induced intestinal mucositis.
Wistar rats received methotrexate (2.5 mg/kg/day for 3 days, subcutaneously) or saline. After 1, 3 and 7 days, sections of duodenum, jejunum and ileum were removed for assessment of epithelial damage and myeloperoxidase activity (biochemical marker of granulocyte infiltration). Others rats were pre-treated with methotrexate or saline, gavage-fed after 3 or 7 days with a standard test liquid meal, and sacrificed 10, 20 or 30-min later. Gastric and small intestine dye recoveries were measured by spectrophotometry.
After 3 days of methotrexate, there was an epithelial intestinal damage in all segments, with myeloperoxidase activity increase in both in duodenum and ileum. Seven days after methotrexate, we observed a complete reversion of this intestinal damage. There was an increase in gastric dye recoveries after 10, 20, and 30-min post-prandial intervals after 3 days, but not after 7 days, of methotrexate. Intestine dye recoveries were decreased in the first and second segments at 10 min, in the third at 20 min, and in the second and third at 30 min, only after 3 days of methotrexate treatment.
Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats.
甲氨蝶呤和其他抗癌药物可诱发肠道黏膜炎，这是阻碍甲氨蝶呤进一步增加剂量的最常见限制因素之一。
评估甲氨蝶呤诱发肠道黏膜炎时液体的胃排空和胃肠转运情况。
将Wistar大鼠分为两组，分别皮下注射甲氨蝶呤（2.5mg/kg/天，共3天）或生理盐水。在第1、3和7天，取出十二指肠、空肠和回肠的切片，评估上皮损伤和髓过氧化物酶活性（粒细胞浸润的生化标志物）。其他大鼠先用甲氨蝶呤或生理盐水预处理，在第3或7天后灌胃给予标准测试流食，10、20或30分钟后处死。通过分光光度法测量胃和小肠的染料回收率。
甲氨蝶呤注射3天后，所有肠段均出现上皮损伤，十二指肠和回肠的髓过氧化物酶活性均增加。甲氨蝶呤注射7天后，我们观察到这种肠道损伤完全恢复。甲氨蝶呤注射3天后，餐后10、20和30分钟时胃染料回收率增加，但7天后未增加。仅在甲氨蝶呤治疗3天后，第10分钟时第一段和第二段、第20分钟时第三段、第30分钟时第二段和第三段的肠染料回收率降低。
甲氨蝶呤诱发的肠道黏膜炎会延迟清醒大鼠的胃排空和液体的胃肠转运。
