title: 5-fluorouracil attenuates dextran sodium sulfate-induced acute colitis in mice.
abstract: 5‑Fluorouracil (5‑FU) has been predominantly used in the clinic for cancer chemotherapy. Previous studies have demonstrated that 5‑FU has an anti‑inflammatory function. In the current study, the potential therapeutic role of 5‑FU in dextran sodium sulfate (DSS)‑induced acute mouse colitis was investigated. Effects on the severity of colitis were studied via histochemical and immunohistochemical staining, cytokine levels were determined by reverse transcriptoin‑quantitative polymerase chain reaction and the effect of 5‑FU on NF‑κB was examined by western blotting. Administration of 5‑FU ameliorated the severity of acute DSS‑induced colitis. The disease activity score was significantly lower in the 5‑FU + DSS‑treated mice compared with the DSS‑treated group (P<0.01). Tumor necrosis factor‑α, interleukin‑1β and interferon γ mRNA expression levels were significantly downregulated in the colon tissue of DSS mice treated with 5‑FU compared with the untreated DSS mice (P<0.05). In addition, the number of CD4+ T cells in the colonic lamina propria and myeloperoxidase activity were significantly decreased in the 5‑FU + DSS‑treated mice (P<0.05). Furthermore, 5‑FU treatment significantly reduced p‑NF‑κB‑p56 protein expression levels in the colon tissue of DSS‑treated mice (P<0.05). The present results demonstrated that 5‑FU minimizes the abnormal immune cytokine response and relieves the pathophysiological disorders associated with experimental acute colitis. Thus, the modulating inflammatory response role of 5‑FU may be partially associated with inhibiting NF‑κB activation and 5‑FU may be a novel therapeutic strategy for the treatment of inflammatory bowel disease.
authors: Department of Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai 200092, P.R. China.
authors: Junhua
authors: J
authors: Xiao
authors: Department of Gastroenterology, The First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
authors: Zhanjun
authors: Z
authors: Lu
authors: Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors: Jiaqing
authors: J
authors: Sheng
authors: Department of Gastroenterology, The First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
authors: Yunna
authors: Y
authors: Song
authors: Department of Gastroenterology, The First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
authors: Weiliang
authors: W
authors: Jiang
authors: Department of Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai 200092, P.R. China.
authors: Fei
authors: F
authors: Liu
authors: Department of Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai 200092, P.R. China.
authors: Ping
authors: P
authors: Zheng
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D016264:Dextran Sulfate; D004353:Drug Evaluation, Preclinical; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology* / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000201:enzymology / Q000276:immunology; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D016264:Dextran Sulfate; D009195:Peroxidase; D005472:Fluorouracil