title: 5-Fluorouracil-induced changes of intestinal integrity biomarkers in BALB/c mice.
abstract: BACKGROUND
  Intestinal mucositis is a most frequently occurring toxicity in cancer chemotherapy, and consequent malnutrition reduces tolerance to cancer therapies. Therefore it is important to lessen the severity of mucotitis and to develop complementary agents capable of reducing mucotitis-related symptoms. This study was conducted to determine 5-fluorouracil (5-FU) induced intestinal damage to understand intestinal damages due to chemotherapy and to provide information on biomarkers which can be used to screen complementary agents in future studies.
  
  
  METHODS
  BALB/c mice were divided into three experimental groups and subjected to the intraperitoneal injection of either 100 mg/kg or 200 mg/kg of 5-FU. The third group was used as PBS controls. Body weights and the consistency of the stools were recorded every day, and the animals were sacrificed on the 7th day post 5-FU administration. The expressions of intestinal tight junction proteins and mRNAs of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) were determined.
  
  
  RESULTS
  The body weight of the animals treated with 5-FU was significantly decreased in a dose-dependent manner. However, mice given 100 mg/kg 5-FU rapidly recovered the original body weight. Symptom of diarrhea was also more severe in 200 mg/kg 5-FU treated group than that of the 100 mg/kg 5-FU treated animals. The expressions of occludin and claudin-1, not ZO-1 protein expressions in 200 mg/kg 5-FU treated animals were significantly reduced compared to those of the control group or 100 mg/kg 5-FU group. The expression of Nuclear factor-kappa B p65 (NF-κB p65) protein and TNF-α mRNA were significantly higher in 5-FU treated group compared to those of control group. No difference was observed with IL-1β expression.
  
  
  CONCLUSIONS
  These results suggested that selected tight junction proteins and inflammatory cytokines are related to 5-FU induced mucositis, and thereby can be used as targets of developing complementary agents.
authors.affiliation: Department of Food and Nutrition, Sookmyung Women's University, Seoul, Korea.
authors.forename: Min-Kyung
authors.initials: MK
authors.lastname: Song
authors.affiliation: Department of Food and Nutrition, Sookmyung Women's University, Seoul, Korea.
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Park
authors.affiliation: Department of Food and Nutrition, Sookmyung Women's University, Seoul, Korea.
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Sung
keywords: 5-Fluorouracil; Chemotherapy; Cytokines; Mucotitis; Tight junction protein