Low detoxification capacity in the ileal pouch mucosa of patients with ulcerative colitis

Background: An ileal pouch-anal anastomosis has become the most widely accepted procedure for surgical treatment of patients with ulcerative colitis (UC). The primary function of the ileum within the pouch changes from absorption to storage. Malignancies have been described in the pouch mucosa. The detoxifying glutathione S-transferase (GST) enzymes are involved in the mucosal protection against toxins and carcinogens. Levels of GSTs are much higher in the ileum as compared with the colon. The adaptation of the ileal pouch mucosa into a more colon-like phenotype possibly influences the activity and levels of GST. This study compares the detoxification capacity of GST of the afferent ileal limb mucosa with the ileal pouch mucosa of patients with UC. Methods: Biopsies from normal-appearing mucosa from the ileal pouch and the ileal afferent limb were obtained from 18 patients with UC. GST isoforms were quantified by immunoblotting. GST activity was measured spectrophotometrically, and glutathione and cysteine levels were determined by high-performance liquid chromatography. Results: The GST activity and GSTA1+A2 levels were significantly lower in the pouch compared with the afferent ileal limb of patients with UC, whereas the GSTP1 levels were higher in the pouch. No differences were observed in the levels of GSTM1, GSTT1, glutathione, or cysteine. Conclusions: The lower GST detoxification activity in the pouch mucosa of patients with UC may result in higher levels of toxins and carcinogens and thus partly contribute to the risk of developing malignancies in the pouch.