title: Protective effect of amifostine on high-dose methotrexate-induced small intestinal mucositis in mice.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  We aimed to evaluate the protective effect of amifostine against high-dose methotrexate-induced small intestinal mucositis and its mechanism.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Outpatient, The First Affiliated Hospital of Zhengzhou University, No.1 East Road Jianshe, Zhengzhou, 450052, Henan Province, China, changying000@126.com.
authors: Changying
authors: C
authors: Chen
authors: Li
authors: L
authors: Tian
authors: Mingzhi
authors: M
authors: Zhang
authors: Qiaozhi
authors: Q
authors: Sun
authors: Xudong
authors: X
authors: Zhang
authors: Xiaodan
authors: X
authors: Li
authors: Xiaoqin
authors: X
authors: Cao
authors: Qianqian
authors: Q
authors: Liu
authors: Xiang
authors: X
authors: Li
authors: Li
authors: L
authors: Hao
mesh_terms: D004999:Amifostine / Q000627:therapeutic use*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005260:Female; D007166:Immunosuppressive Agents / Q000633:toxicity; D007421:Intestine, Small / Q000187:drug effects* / Q000473:pathology; D002955:Leucovorin / Q000494:pharmacology; D008297:Male; D008727:Methotrexate / Q000633:toxicity*; D051379:Mice; D052016:Mucositis / Q000139:chemically induced* / Q000188:drug therapy*; D011837:Radiation-Protective Agents / Q000494:pharmacology; D011897:Random Allocation; D013047:Specific Pathogen-Free Organisms
chemical_list: D007166:Immunosuppressive Agents; D011837:Radiation-Protective Agents; D004999:Amifostine; D002955:Leucovorin; D008727:Methotrexate
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