Current Pharmaceutical Design

Author(s): Kikuko Amagase, Yuki Kimura, Akimitsu Wada, Tohru Yukishige, Toshiko Murakami, Eiji Nakamura and Koji Takeuchi

DOI: 10.2174/13816128113199990579

Prophylactic Effect of Monosodium Glutamate on NSAID-Induced Enteropathy in Rats

Page: [2783 - 2790] Pages: 8

  • * (Excluding Mailing and Handling)

Abstract

We reviewed the prophylactic effect of monosodium glutamate (MSG), a substance known as the “umami”, on NSAIDinduced 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.

Keywords: Monosodium glutamate, loxoprofen, small intestinal lesion, prophylactic effect, rat.