DSS-induced acute colitis in C57BL/6 mice is mitigated by sulforaphane pre-treatment.
The Brassica-derived isothiocyanate sulforaphane (SFN) is known to induce factor erythroid 2-related factor 2 (Nrf2), a transcription factor centrally involved in chemoprevention. Furthermore, SFN exhibits anti-inflammatory properties in vitro and in vivo. However, little is known regarding the anti-inflammatory properties of SFN in severe inflammatory phenotypes. In the present study, we tested if pre-treatment with SFN protects mice from dextran sodium sulphate (DSS)-induced colitis. C57BL/6 mice received either phosphate-buffered saline (control) or 25 mg/kg body weight (BW) SFN per os for 7 days. Subsequently, acute colitis was induced by administering 4% DSS via drinking water for 5 days and BWs, stool consistency and faecal blood loss were recorded. Following endoscopic colonoscopy, mice were sacrificed, the organs excised and spleen weights and colon lengths measured. For histopathological analysis, distal colon samples were fixed in 4% para-formaldehyde, sectioned and stained with hematoxylin/eosin. Inflammatory biomarkers were also measured in distal colon. Treatment with SFN prior to colitis induction significantly minimised both BW loss and the disease activity index compared to control mice. Furthermore, colon lengths in SFN pre-treated mice were significantly longer than in control mice. Both macroscopic and microscopic analysis of the colon revealed attenuated inflammation in SFN pre-treated animals. mRNA analysis of distal colon samples confirmed reduced expression of inflammatory markers and increased expression of Nrf2-dependent genes in SFN pre-treated mice. Our results indicate that pre-treating mice with SFN confers protection from DSS-induced colitis. These protective effects were corroborated macroscopically, microscopically and at the molecular level.
Institute of Human Nutrition and Food Science, Christian-Albrechts-University Kiel, 24118 Kiel, Germany. Electronic address: wagner@molecularnutrition.uni-kiel.de.
Anika E
AE
Wagner
Olga
O
Will
Christine
C
Sturm
Simone
S
Lipinski
Philip
P
Rosenstiel
Gerald
G
Rimbach
D000818:Animals; D015415:Biomarkers / Q000097:blood; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D016264:Dextran Sulfate / Q000009:adverse effects*; D017879:Isothiocyanates / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D013454:Sulfoxides
D015415:Biomarkers; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D013454:Sulfoxides; D016264:Dextran Sulfate; C016766:sulforaphane
Colitis; Inflammation; NFκB; Nrf2; Sulforaphane