New Therapeutic Strategy for Amino Acid Medicine: Prophylactic and Healing Promoting Effect of Monosodium Glutamate Against NSAID-Induced Enteropathy

Abstract

Abstract.We reviewed the effect of monosodium glutamate (MSG) on the development and healing of nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal lesions in rats. Loxoprofen (60 mg/kg, p.o.) induced lesions in the small intestine within 24 h, accompanied by a decrease of Muc2 expression and an increase in enterobacterial invasion and inducible nitric oxide synthase (iNOS) expression. These lesions were prevented when MSG was given as a mixture of powdered food for 5 days before the loxoprofen treatment. This effect of MSG was accompanied by an increase in Muc2 expression / mucus secretion as well as the suppression of bacterial invasion and iNOS expression. These intestinal lesions healed spontaneously within 6 days, but the process was impaired by the repeated administration of low-dose loxoprofen (30 mg/kg) for 5 days after the ulceration, with the decrease of vascular endothelial derived growth factor (VEGF) expression and angiogenesis. The healing-impairing effect of loxoprofen was prevented by feeding 5% MSG for 5 days after the ulceration. These results suggest that MSG not only prevents loxoprofen-induced small intestinal damage but also promotes a healing of these lesions; the former is functionally associated with the increase in Muc2 expression / mucus secretion and the suppression of bacterial invasion and iNOS expression, while the latter is associated with the stimulation of VEGF expression/angiogenesis.

Dipeptidyl Peptidase IV Inhibition Prevents the Formation and Promotes the Healing of Indomethacin-Induced Intestinal Ulcers in Rats

“…Feeding of L-Glu (1 or 5 %) for 5 days prior to one time NSAID treatment significantly reduced intestinal lesions while daily treatment for 5 days with L-Glu after NSAID treatment accelerated ulcer healing [50], consistent with our finding that luminal amino acids prevent the formation and promote healing of NSAID-induced enteropathy, although one dose of L-Glu/IMP did not significantly inhibit ulcer formation in our study. The combination of metformin, which increases the release of GLP-1 and 2, with a DPPIV inhibitor, prevents 5-fluorouracil-induced mucositis [51].…”

Nutritional and Physiological Significance of Luminal Glutamate-sensing in the Gastrointestinal Functions

“…He clearly showed that glutamate-supplemented foods could protect non-steroid anti-in‰ammatory drug (NSAID)-induced gastric and duodenal ulcers in rat models. 54) The protective eŠects of glutamate were observed in H. pylori infected-gastric ulcers in the gerbil. 55) Oral care Saliva is essential for the maintenance of oral mucosa circumstances as well as oral functions such as speech, mastication, swallowing and taste sensation.…”

Beneficial Effects of an Amino Acid Mixture on Colonic Mucosal Healing in Rats

“…12 Glutamate, an amino acid whose metabolism is tightly related to glutamine metabolism in intestinal epithelial cells, 13 has been reported to promote small intestine MH after chemically induced enteropathy in rats. 14 Glutamate and glutamine are well known to be major fuels from the arterial origin for colonic epithelial cells. They are intensely oxidized by these cells 15,16 in a context of high energy requirement for the colonic epithelium renewal, thus requiring intense anabolic metabolism.…”