Z Gastroenterol 2005; 43 - 110
DOI: 10.1055/s-2005-869757

Protective effect of lactulose on dextran sulfate sodium-induced colonic inflammation in rats

Gy Rumi 2, R Tsubouchi 1, M Okayama 1, S Kato 1, Gy Mózsik 2, B Hunyady 2, K Takeuchi 1
  • 1Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmacological University, Yamashina, Kyoto, Japan
  • 21st Department of Medicine, Medical Faculty of Pecs University, Pecs, Hungary

Background/Aim: Intestinal microflora is likely an important initiating factor in the pathogenesis of ulcerative colitis (UC). Promising results have recently been obtained with probiotic therapy in UC. Orally administered lactulose has been shown to increase the colonic levels of Lactobacillus species associated with probiotic activity. The purpose of the present study was to examine the effect of lactulose on a rat UC model induced by dextran sulfate sodium (DSS).

Methods: Experimental colitis was induced in male Wistar rats by 3% DSS-solution added to drinking water for 7 days. Lactulose (300–1000mg/kg) was administered PO twice daily for 6 days. Colonic ulceration area, colon length, body weight changes, diarrhea/bloody feces, colonic mucosal myeloperoxidase activity (MPO), thiobarbituric acid reactive substances (TBARS) and histology were examined.

Results: DSS-treatment of control animals resulted in severe colonic lesions accompanied by diarrhea, bloody feces, decrease of body weight, shortening of colon length, and increase in MPO activity as well as TBARS, compared to normal rats. Lactulose treatment ameliorated DSS-induced colitis in a dose-dependent manner, and at 1000mg/kg all of the parameters examined, except TBARS, were shown to improve significantly as compared to controls. The mucosal damage scores in the groups treated with 300, 600 and 1000mg/kg of lactulose were 186.6±65, 175.9±61.1, 109.3±46.5 mm2, respectively, the last two being significantly lower (p<0.01) as compared to the control value (287.3±44.1 mm2). A dose-dependent and significant (p<0.01) inhibition of DSS-induced colon shortening was also observed in all lactulose-treated groups, while the MPO activity was significantly (p<0.01) reduced by only 1000mg/kg of lactulose. The microscopical grading in the severity of damage was remarkably reduced by lactulose.

Conclusion: These results demonstrated the protective effect of lactulose in this rat colitis model and suggested that the background of this lactulose effect may be due to alterations of colonic microflora. The ongoing determination of the changes in colonic microflora induced by lactulose may clarify the mechanism of action.