Protective effect of lactulose on dextran sulfate sodium-induced colonic inflammation in rats.
Promising results have recently been obtained with pre- and probiotic therapy in ulcerative colitis (UC). The prebiotic potential of lactulose is well established, but it has not yet been investigated in experimental colitis models. The purpose of the study was to examine the effect of lactulose on an UC model induced by 3% dextran sulfate sodium (DSS) solution added to drinking water for 7 days in male Wistar rats. Lactulose (300-1000 mg/kg) or 5-aminosalicylic acid (5-ASA; 150 mg/kg) was administered orally 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. Treatment of animals with DSS for 7 days resulted in severe colonic lesions accompanied by diarrhea, bloody feces, a decrese in body weight, shortening of the colon length, and an 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 1000 mg/kg all of the parameters examined, except TBARS, were shown to improve significantly as compared to controls. Daily administration of 5-ASA also significantly reduced the severity of colonic lesions following DSS treatment. 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.
Rumi
György
G
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmacological University, Yamashina, Kyoto, Japan. rumigy@yahoo.com
Tsubouchi
Ryouichi
R
Okayama
Mitsuaki
M
Kato
Shinichi
S
Mózsik
Gyula
G
Takeuchi
Koji
K
D000818:Animals; D001707:Biopsy, Needle; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000517:prevention & control; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000032:analysis; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology*; D007792:Lactulose / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D011336:Probability; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D012680:Sensitivity and Specificity
D018836:Inflammation Mediators; D020011:Protective Agents; D007792:Lactulose; D016264:Dextran Sulfate; D009195:Peroxidase