title: Preventative Effects of Sodium Alginate on Indomethacin-induced Small-intestinal Injury in Mice.
abstract: Recent advances in diagnostic technologies have revealed that nonsteroidal anti-inflammatory drugs (NSAIDs) can cause serious mucosal injury in the upper and lower gastrointestinal tract (including the small intestine). A drug to treat NSAID-induced small-intestinal injury (SII) is lacking. Sodium alginate is a soluble dietary fiber extracted from brown seaweed and its solution has been used as a hemostatic agent to treat gastrointestinal bleeding due to gastric ulcers. Whether sodium alginate has therapeutic effects on NSAID-induced SII and its mechanism of action are not known. Here, we investigated if administration of two forms (high-molecular-weight (HMW) and low-molecular-weight (LMW)) of sodium alginate could ameliorate indomethacin-induced SII. Pretreatment with HMW sodium alginate or LMW sodium alginate before indomethacin administration improved ulceration and the resultant intestinal shortening was associated with reduced histological severity of mucosal injury and ameliorated mRNA expression of inflammation-related molecules in the small intestine. We found that mRNAs of secretory Muc2 and membrane-associated Muc1, Muc3 and Muc4 were expressed in the small intestine. mRNA expression of Muc1-4 was increased in indomethacin-induced SII, and these increases were prevented by sodium alginate. Thus, administration of sodium alginate could be a therapeutic approach to prevent indomethacin-induced SII.
authors.affiliation: Department of Medical Pharmaceutics, Kobe Pharmaceutical University, Kobe 658-8558, Japan;
authors.forename: Sayo
authors.initials: S
authors.lastname: Horibe
authors.affiliation: Department of Medical Pharmaceutics, Kobe Pharmaceutical University, Kobe 658-8558, Japan;; Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Toshihito
authors.initials: T
authors.lastname: Tanahashi
authors.affiliation: Educational Center for Clinical Pharmacy, Kobe Pharmaceutical University, Kobe 658-8558, Japan;
authors.forename: Shoji
authors.initials: S
authors.lastname: Kawauchi
authors.affiliation: Department of Medical Pharmaceutics, Kobe Pharmaceutical University, Kobe 658-8558, Japan;; Endoscopy Department, Kindai University Nara Hospital, Ikoma 630-0293, Japan;
authors.forename: Shigeto
authors.initials: S
authors.lastname: Mizuno
authors.affiliation: Department of Medical Pharmaceutics, Kobe Pharmaceutical University, Kobe 658-8558, Japan;; Division of Signal Transduction, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Rikitake
mesh_terms: D000464:Alginates / Q000008:administration & dosage*; D000818:Animals; D004195:Disease Models, Animal; D005769:Gastrointestinal Motility / Q000187:drug effects; D020723:Glucuronic Acid / Q000008:administration & dosage; D006603:Hexuronic Acids / Q000008:administration & dosage; D006801:Humans; D007213:Indomethacin / Q000009:adverse effects; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects* / Q000293:injuries; D051379:Mice; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D020723:Glucuronic Acid; D007213:Indomethacin
keywords: gene expression; mucin; nonsteroidal anti-inflammatory drugs; small intestine; sodium alginate.