glutaminase and Crohn-Disease

Topics: Adult; Animals; Colitis; Crohn Disease; Female; Glutaminase; Humans; Interleukin-10; Intestines; Lymphocyte Subsets; Male; Mechanistic Target of Rapamycin Complex 1; Mice, Inbred C57BL; Sulfides; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory; Thiadiazoles

Intestinal glutamine utilization is integral to mucosal regeneration. We analyzed the systemic and intestinal glutamine status in Crohn's disease (CD) and evaluated the therapeutic effect of glutamine supplementation in an animal model of ileitis. In CD, glutamine concentrations were decreased systemically and in noninflamed and inflamed ileal/colonic mucosa. Mucosal glutaminase activities were depressed in the ileum independent of inflammation but were not different from controls in the colon. In experimental ileitis, oral glutamine feeding prevented macroscopic inflammation, enhanced ileal and colonic glutaminase activities above controls, and normalized the intestinal glutathione redox status. However, glutamine supplementation enhanced myeloperoxidase activity along the gastrointestinal tract and potentiated lipid peroxidation in the colon. In conclusion, glutamine metabolism is impaired in CD. In experimental ileitis, glutamine supplementation prevents inflammatory tissue damage. In the colon, however, which does not use glutamine as its principal energy source, immune enhancement of inflammatory cells by glutamine increases oxidative tissue injury.

Topics: Adult; Animals; Case-Control Studies; Colon; Crohn Disease; Dietary Supplements; Disease Models, Animal; Enteral Nutrition; Female; Glutaminase; Glutamine; Glutathione; Humans; Ileitis; Ileum; Indomethacin; Intestinal Mucosa; Lipid Peroxidation; Male; Middle Aged; Rats; Rats, Sprague-Dawley; Rectus Abdominis