Preventive and therapeutic effects of nitrite supplementation in experimental inflammatory bowel disease.
BACKGROUND
Inorganic nitrate and nitrite have emerged as alternative substrates for nitric oxide (NO) generation in the gastrointestinal tract, and have shown to be protective against drug-induced gastric injury. The aim of this study was to investigate the preventive and therapeutic effects of nitrate and nitrite in a model of experimental colitis.


METHODS
Colitis was induced in mice by administrating dextran sulfate sodium (DSS) with concurrent administration of nitrite (1 mM) or nitrate (10 mM) in the drinking water for 7 days. A therapeutic approach was also investigated by initiating nitrite treatment 3 days after DSS-induced colitis. Clinical and inflammatory markers were assessed and the colonic mucus thickness was measured in vivo. The effect of nitrite on wound healing was evaluated using colon epithelial cells.


RESULTS
Concurrent administration of DSS and nitrite (1 mM) alleviated inflammation as determined by reduced disease activity index score (DAI) and increased colon length, while nitrate (10 mM) only reduced the DAI-score. Nitrite also displayed therapeutic effects by ameliorating established colonic inflammation with reduced colonic expression of iNOS and improving histopathology. DSS-induced decrease in colonic mucus thickness was completely prevented by nitrite administration. In addition, goblet cell abundance was lower by DSS treatment, but was increased by addition of nitrite. Further studies using colon epithelial cells revealed an NO-dependent improvement in wound healing with nitrite administration.


CONCLUSIONS
Nitrite exerts both preventive and therapeutic effects in colonic inflammation. The protective effects involve preservation of an intact adherent mucus layer and regulation of epithelial cell restitution.
Department of Pharmacology and Physiology, Karolinska Institute, Sweden.
Cecilia
C
Jädert
Department of Medical Cell Biology, Uppsala University, Sweden.
Mia
M
Phillipson
Department of Medical Cell Biology, Uppsala University, Sweden.
Lena
L
Holm
Department of Pharmacology and Physiology, Karolinska Institute, Sweden.
Jon O
JO
Lundberg
Department of Pharmacology and Physiology, Karolinska Institute, Sweden.
Sara
S
Borniquel
D000818:Animals; D002460:Cell Line; D003092:Colitis / Q000139:chemically induced / Q000178:diet therapy* / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects; D016264:Dextran Sulfate; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009566:Nitrates / Q000008:administration & dosage* / Q000627:therapeutic use; D009573:Nitrites / Q000008:administration & dosage* / Q000627:therapeutic use; D014945:Wound Healing / Q000187:drug effects
D009566:Nitrates; D009573:Nitrites; D016264:Dextran Sulfate
DSS; Inflammatory bowel disease; Mucus; Nitrate; Nitrite