title: Prophylactic effect of monosodium glutamate on NSAID-induced enteropathy in rats.
abstract: We reviewed the prophylactic effect of monosodium glutamate (MSG), a substance known as the "umami", on NSAID-induced small intestinal damage in rats. Loxoprofen, one of the NSAIDs frequently used in Asian countries, given orally at 60 mg/kg, caused hemorrhagic damage in the small intestine, mainly jejunum and ileum, concomitant with a down-regulation of Muc2 expression/ mucus secretion and an up-regulation of enterobacterial invasion and neutrophil migration as well as inducible nitric oxide synthase (iNOS) expression. The severity of these lesions was reduced by pretreatment with MSG (0.1~5%) given as a mixture of powder food (10 g/rat/day) for 5 days before administration of loxoprofen. The effect of MSG was accompanied by an up-regulation of Muc2 expression/ mucus secretion as well as a suppression of bacterial invasion, iNOS expression and myeloperoxidase activity. On the other hand, these lesions spontaneously healed within 7 days, but this process was hampered by loxoprofen at low doses (>10 mg/kg) given repeatedly for 5 days after ulceration. The healing-impairment effect of loxoprofen was accompanied by the down-regulation of vascular endothelium- derived growth factor (VEGF) expression and angiogenic response, and these responses were all antagonized by feeding diet containing 5% MSG for 5 days after ulceration. It is suggested that MSG exhibits a prophylactic effect against loxoprofen-induced small intestinal lesions, this effect is functionally associated with the up-regulation of Muc2 expression/mucus secretion, resulting in suppression of enterobacterial invasion and iNOS expression, the major pathogenic events in NSAID-induced enteropathy, and MSG also has the healing promoting effect on these lesions through enhancement of VEGF expression and angiogenesis.
authors.forename: Kikuko
authors.initials: K
authors.lastname: Amagase
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kimura
authors.forename: Akimitsu
authors.initials: A
authors.lastname: Wada
authors.forename: Tohru
authors.initials: T
authors.lastname: Yukishige
authors.forename: Toshiko
authors.initials: T
authors.lastname: Murakami
authors.forename: Eiji
authors.initials: E
authors.lastname: Nakamura
authors.affiliation: Department of Pharmacology and Experimental therapeutics, Division of Pathological Sciences, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan. takeuchi@mb.kyoto-phu.ac.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Takeuchi
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007410:Intestinal Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D007421:Intestine, Small / Q000187:drug effects / Q000473:pathology; D010666:Phenylpropionates / Q000633:toxicity*; D051381:Rats; D012970:Sodium Glutamate / Q000008:administration & dosage*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010666:Phenylpropionates; C040656:loxoprofen; D012970:Sodium Glutamate