Oral administration of taurolidine ameliorates chronic DSS colitis in mice.
Taurolidine (TRD) has antimicrobial and anti-inflammatory properties. However, the anti-inflammatory effects of TRD in inflammatory bowel diseases (IBD) have not been investigated. Here, we have analyzed the toxicity of TRD after oral long-term application in mice and examined the impact of oral TRD in a dextran sulfate sodium (DSS) model of experimental colitis. Female C57/BL6 mice received TRD in various concentrations (0.1% to 0.4%) for 60 days. Toxicity was evaluated by use of a disease activity index (DAI) and histological examination of major metabolic organs. Furthermore, the impact of 0.2% TRD on a chronic DSS colitis was examined by daily DAI, histological crypt damage score (CDS), bacterial translocation into mesenteric lymph nodes (MLN), and colonic expression of tumor necrosis factor (TNF) alpha, transforming growth factor (TGF) beta, interleukin (IL)-1beta, IL-6, cytochrome oxidase (COX)-2, and monocyte chemotactic protein (MCP)-1 by real-time polymerase chain reaction (PCR). Oral TRD administration for 60 days was well tolerated by the animals and did not show any toxic effects in terms of DAI and histological changes. TRD treatment of DSS colitis led to increased survival of 100%, compared to 33% in the untreated colitis group (p < or = .005). Clinical amelioration was mirrored by significantly reduced DAI and CDS in the TRD treated colitis. Colonic cytokine expression and bacterial translocation into MLN showed no differences between both groups. We thus report for the first time that oral application of TRD results in amelioration of an experimental IBD model. We hypothesize direct intraluminal antimicrobial effects of TRD as well as anti-inflammatory effects during the acute phase of DSS colitis.
Chromik
Ansgar Michael
AM
Department of General and Visceral Surgery, St Josef Hospital, Ruhr-University of Bochum, Bochum, Germany. a.chromik@klinikum-bochum.de
Müller
Annette M
AM
Albrecht
Martin
M
Rottmann
Sabrina
S
Otte
Jan-Michel
JM
Herdegen
Thomas
T
Uhl
Waldemar
W
Mittelkötter
Ulrich
U
D000284:Administration, Oral; D000818:Animals; D018988:Bacterial Translocation; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D003106:Colon / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D016264:Dextran Sulfate; D005260:Female; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008198:Lymph Nodes / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D013654:Taurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013829:Thiadiazines / Q000008:administration & dosage / Q000627:therapeutic use*
D016207:Cytokines; D013829:Thiadiazines; D013654:Taurine; C012566:taurolidine; D016264:Dextran Sulfate; D051546:Cyclooxygenase 2