Protective Effect of Amifostine on High-Dose Methotrexate-Induced Small Intestinal Mucositis in Mice

被引:34
作者
Chen, Changying [1 ]
Tian, Li [2 ]
Zhang, Mingzhi [2 ]
Sun, Qiaozhi [2 ]
Zhang, Xudong [2 ]
Li, Xiaodan [3 ]
Cao, Xiaoqin [3 ]
Liu, Qianqian [2 ]
Li, Xiang [2 ]
Hao, Li [1 ]
机构
[1] Zhengzhou Univ, Affiliated Hosp 1, Dept Outpatient, Zhengzhou 450052, Henan Province, Peoples R China
[2] Zhengzhou Univ, Affiliated Hosp 1, Inst Clin Med, Dept Oncol, Zhengzhou 450052, Henan Province, Peoples R China
[3] Zhengzhou Univ, Affiliated Hosp 1, Dept Cardiovasc, Zhengzhou 450052, Henan Province, Peoples R China
关键词
Methotrexate; Amifostine; Chemotherapy; Intestinal mucositis; ORAL CRYOTHERAPY; CONTROLLED-TRIAL; RADIATION; CHEMOTHERAPY; CANCER; THERAPY; TOXICITY; LEUKEMIA; BCL-2;
D O I
10.1007/s10620-013-2826-3
中图分类号
R57 [消化系及腹部疾病];
学科分类号
100201 [内科学];
摘要
Amifostine has been shown to be capable of minimizing radiotherapy-induced oral mucositis, but whether it protects small intestinal mucosae from high-dose methotrexate-induced damage is presently unknown. We aimed to evaluate the protective effect of amifostine against high-dose methotrexate-induced small intestinal mucositis and its mechanism. Ninety Kunming mice were randomly divided into five experimental groups: saline control; high-dose methotrexate (HDMTX) group: treated with a single high dose of methotrexate; calcium folinate (CF) group: treated with high-dose methotrexate followed with CF; Amifostine group: treated with amifostine, followed with high-dose methotrexate; and amifostine-CF group: treated with amifostine pre-high-dose methotrexate and followed by CF post-high-dose methotrexate. Mouse weight, villus height and crypt depth, stool consistency, white blood cell count, death and survival were recorded. Bax and Bcl-2 mRNA expression were quantified by semi-quantitative PCR. Compared to the mice treated with HDMTX, CF, and amifostine, mice treated with Amifostine-CF group were heavier and had greater villus height, crypt depth, and normal white blood cell count and lower diarrhea rate and mortality than the HDMTX, CF and amifostine groups. There was a significant decrease in enterocyte apoptosis in amifostine-CF mice compared with the HDMTX and CF groups. The effect of amifostine plus CF was greater than amifostine or CF alone in preventing high-dose methotrexate-induced intestinal mucositis and improving intestinal recovery in mice.
引用
收藏
页码:3134 / 3143
页数:10
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