Preventative effects of lactulose in the trinitrobenzenesulphonic acid model of rat colitis.
OBJECTIVE
Lactulose is a drug used as a laxative that has been shown to promote the growth of lactobacilli and bifidobacteria, acting as a prebiotic and with a potential beneficial effect in inflammatory bowel disease. The present study describes the preventive antiinflammatory activity of lactulose in the trinitrobenzenesulphonic acid (TNBS) model of rat colitis.


METHODS
Rats were rendered colitic by a colonic instillation of 10 mg of TNBS dissolved in 0.25 mL of 50% ethanol. One group of colitic rats received lactulose, which was incorporated in the drinking water (2.5% wt/vol) for 2 weeks before TNBS instillation, and colonic damage was evaluated 1 week after colitis induction. Different biochemical markers of colonic inflammation were assayed: myeloperoxidase activity, glutathione content, tumor necrosis factor alpha, leukotriene B4 levels, and colonic inducible nitric oxide synthase expression. In addition, bacterial counts (for lactobacilli and bifidobacteria) were performed in colonic contents from colitic rats.


RESULTS
The results show that lactulose exerted a preventive antiinflammatory effect in this model of rat colitis, as evidenced by a significant reduction of myeloperoxidase activity and by a decrease of both colonic tumor necrosis factor alpha and leukotriene B4 production. This effect was also characterized by an inhibition of colonic inducible nitric oxide synthase expression, which is unregulated as a consequence of the inflammatory status. This beneficial effect was associated with increased levels of lactobacilli and bifidobacteria species in colonic contents in comparison with untreated colitic rats.


CONCLUSIONS
In conclusion, the intestinal antiinflammatory effect of lactulose could be related to its prebiotic properties, supporting its potential use in human inflammatory bowel disease.
Camuesco
Desiree
D
Department of Pharmacology, School of Pharmacy, University of Granada, Granada, Spain.
Peran
Laura
L
Comalada
Monica
M
Nieto
Ana
A
Di Stasi
Luiz C
LC
Rodriguez-Cabezas
M Elena
ME
Concha
Angel
A
Zarzuelo
Antonio
A
Galvez
Julio
J
D000818:Animals; D003092:Colitis / Q000188:drug therapy* / Q000517:prevention & control* / Q000662:veterinary; D004195:Disease Models, Animal; D005260:Female; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D007777:Lactobacillaceae / Q000254:growth & development; D007792:Lactulose / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000096:biosynthesis; D009195:Peroxidase / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014302:Trinitrobenzenesulfonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D007975:Leukotriene B4; D007792:Lactulose; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase