Effects of proteoglycan on dextran sulfate sodium-induced experimental colitis in rats.
Proteoglycans (PG) are macromolecules composed of glycosaminoglycan chains covalently attached to a protein core. In this study, we examined the effects of PG on dextran sulfate sodium (DSS)-induced experimental colitis in rats. First, to examine whether PG may ameliorate acute established DSS colitis, PG was administered orally for 5 days to the model animals. We evaluated the effects of PG on the basis of clinical symptoms, hematological analysis, macroscopic observation, and microscopic examination. We then examined whether PG administered orally to rats was detectable in their colonic lumen. After administration of PG, the colonic contents were collected, and the molecular weight of PG in the sample was analyzed by gel filtration high-performance liquid chromatography. Furthermore, we examined whether orally administered PG affected the concentrations of short-chain fatty acids (SCFAs) in the colonic feces. Orally administered PG ameliorated the clinical symptoms of bloody stools and diarrhea, and attenuated the increase in the white blood cell count in rats with established DSS colitis. Histologically, orally administered PG reduced the degree of mucosal erosion and inflammatory cell infiltration into the erosive area induced by DSS. Orally administered PG was detected in rat colon, although its molecular weight was slightly decreased. Orally administered PG significantly increased the concentration of total SCFAs and n-butyrate in rat colonic feces. This is the first study to indicate that exogenous PG ameliorates experimental colitis, suggesting the potential usefulness of PG for clinical treatment of colitis.
Ota
Sakae
S
Second Department of Surgery, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan. sakaeota@cc.hirosaki-u.ac.jp
Yoshihara
Shuichi
S
Ishido
Keinosuke
K
Tanaka
Masanori
M
Takagaki
Keiichi
K
Sasaki
Mutsuo
M
D000284:Administration, Oral; D000818:Animals; D002087:Butyrates / Q000032:analysis; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000473:pathology*; D016264:Dextran Sulfate; D003967:Diarrhea / Q000188:drug therapy; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005232:Fatty Acids, Volatile / Q000032:analysis; D005243:Feces / Q000737:chemistry; D008297:Male; D011509:Proteoglycans / Q000008:administration & dosage / Q000032:analysis / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D002087:Butyrates; D005232:Fatty Acids, Volatile; D011509:Proteoglycans; D016264:Dextran Sulfate