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Evidence for intestinal oxidative stress in patients with obstructive jaundice

Authors


  • Department of Internal Medicine, School of Medicine (S. F. Assimakopoulos); Department of Internal Medicine, Division of Gastroenterology, School of Medicine (K. C. Thomopoulos, V. N. Nikolopoulou); Department of Biology, Division of Genetics, Cell and Developmental Biology (N. Patsoukis, C. D. Georgiou); Department of Pathology, School of Medicine (C. D. Scopa); Department of Surgery, School of Medicine (C. E. Vagianos), University of Patras, Patras, Greece.

Stelios F. Assimakopoulos, Department of Internal Medicine, School of Medicine, University of Patras, PO Box 1174, 261 10 Patras, Greece. Tel.: +30 2610 990 038; fax: +30 2610 990 775; e-mail: sassim@upatras.gr

Abstract

Background  Obstructive jaundice results in failure of the intestinal barrier with consequent systemic endotoxemia associated with septic complications. We have recently shown that gut barrier failure in experimental obstructive jaundice is associated with high intestinal oxidative stress. This study was undertaken to investigate whether oxidative alterations occur in the intestinal mucosa of patients with obstructive jaundice.

Patients and methods  Fifteen patients with malignant biliary obstruction and no signs of cholangitis and 15 control patients were subjected to duodenal biopsy to assess intestinal oxidative stress, estimated by lipid peroxidation (malondialdehyde – MDA) and glutathione redox state [reduced glutathione (GSH), glutathione disulphide (GSSG) and GSH/GSSG ratio]. In addition, mucosal biopsies were examined histologically and intestinal mucosal protein content was determined biochemically as an index of intestinal trophic state.

Results  Patients with obstructive jaundice presented high levels of intestinal oxidative stress, with significantly increased lipid peroxidation (P < 0·001). Glutathione redox state was also suggestive of high intestinal oxidative stress in jaundiced patients, indicated by significantly decreased GSH (P = 0·001) and GSH/GSSG ratio (P = 0·006) and increased GSSG (P = 0·026). Histological examination showed a mild infiltration of the lamina propria by chronic inflammatory cells in obstructive jaundice, whereas duodenal architecture remained intact and epithelial continuity was retained. Duodenal mucosa was atrophic in jaundiced patients as indicated by a significant reduction of mucosal protein content compared with controls (P = 0·001). Among oxidative stress parameters, intestinal GSH exhibited a significant positive correlation with mucosal protein content (r = 0·588, P = 0·021).

Conclusions  Obstructive jaundice in humans induces intestinal oxidative stress, which may be a key factor contributing to intestinal barrier failure and the development of septic complications in this patient population.

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