Nutrition Research, Vol. 17. No. 3. 463473. 1997 pp. Copyright 0 1997 Elsevier Science Inc. Printed in the USA. All rights resewed 0271.5317/97 $17.00 + .a3 ELSEVIER PI1 SO271-5317(97)00007-9 GLUTATHIONE LEVELS IN CHRONIC INFLAMMATORY DISORDERS OF THE HUMAN COLON Eduardo A. Ruan, M.D., Simbasiva Rao, M.D., J. Steven Bun-lick, M.D., Steven J. Stryker, M.D., Gordon L. Telford, M.D., Mary F. Otterson, M.D., Emmanuel C. Opara, Ph.D., and Timothy R. Koch, M.D.* Departments of Medicine and Surgery, Zablocki VA Medical Center, Medical College of Wisconsin, Milwaukee, Wisconsin; Departments of Surgery and Pathology, Northwestern University Medical School, Chicago, Illinois; and Duke University Medical Center, Durham, North Carolina ABSTRACT Glutathione depletion has been described in tissues obtained from several chronic diseases. Increased t?ee radical production by inflammatory cells occurs in inflammatory bowel disease. We hypothesized that this could induce depletion of gut antioxidants. In this study, we examined the potential relationship between chronic inflammation and colonic glutathione levels. Using a validated assay, glutathione levels were determined in the mucosal-submucosal layer and the muscularis extema layer in surgical colonic specimens from 26 patients with ulcerative colitis, 14 patients with Crohn’s colitis, and 10 patients who Tunderwent partial colectomy for non-obstructive neoplasia. Inflammation was graded histologically. Glutathione levels were decreased in the muscularis extema and in the mucosal-submucosal layers horn both ulcerative colitis and C&n’s colitis (both p<O.O5). There were parallel declines of glutathione levels in the muscularis extema layer compared to the mucosal-submucosal layer from individual colonic specimens. ln ulcerative colitis, glutathione levels were reduced in histologically active disease compared to inactive disease (in the mucosal-submucosal layers: Mea&SEM were 214*68 nmol/g wet tissue and 808*30, respectively; in the muscularis extema layers: 333*97 and 89&340; both ~4.05). In Crohn’s colitis, there were no significant differences between histologically active and inactive disease (in the mucosal-submucosal layers: 114*53 and 461*206; in the muscularis extema layers: 105*59 and 553*211; both p>O.O5). This study provides evidence that chronic inflammatory disorders of the colon are associated with glutathione depletion. ln ulcerative colitis, there was a relationship between the severity of intlammation and glutathione depletion. By contrast, this relationship was not significant in Crohn’s colitis. The results suggest that there could be a primary defect in glutathione production in Crohn’s colitis, or a difference in the relative levels of free radical production by inflammatory cells present in these two disorders of colonic intlammation. copyn’ght 0 1997 Elsevia scislcc Inc. Key Words: Glutathione, Colon, Crohn’s disease, Ulcerative colitis, Antioxidant, Inflammatory bowel disease. ?? Conqondiig Author: Dr. Timothy R. Koch, Chief, Section of Gastroenterology, Robert C. Byrd Health Sciences Center of West Virginia University, P.O. Box 9161, Morgantown, West Virginia 26506-9161. 463