title: Is intestinal oxidative stress involved in patients with compensated liver cirrhosis?
abstract: BACKGROUND
  Liver cirrhosis is associated with intestinal epithelial barrier dysfunction, which may be affected by oxidative stress. Studies in cirrhotic rats provided evidence for intestinal oxidative stress, but studies in cirrhotic patients are scarce. We have shown intestinal barrier dysfunction in patients with compensated cirrhosis.
  
  
  OBJECTIVE
  The present study aimed to investigate whether oxidative stress occurs in the intestinal mucosa of compensated cirrhotic patients and may contribute to barrier dysfunction.
  
  
  METHODS
  Oxidative stress was studied in duodenal and sigmoid biopsies from 15 cirrhotic patients and 22 controls by analyzing transcription of genes involved in glutathione and uric acid metabolism using quantitative real-time polymerase chain reaction. Protein levels of glutathione and glutathione disulphide were measured and the glutathione/glutathione disulphide ratio was calculated as marker of oxidative stress. In addition, intestinal myeloperoxidase and fecal calprotectin were determined.
  
  
  RESULTS
  Gene transcription of glutathione synthetase and glutathione reductase were significantly different in duodenal and sigmoid biopsies of cirrhotic patients vs. controls, but no alterations were found for other genes nor for glutathione, glutathione disulphide, glutathione/glutathione disulphide ratio and intestinal myeloperoxidase and fecal calprotectin concentrations.
  
  
  CONCLUSIONS
  This study did not find indications for oxidative stress and low-grade inflammation in the small and large intestine of stable compensated cirrhotic patients. Although these preliminary findings need further validation, we found intestinal oxidative stress not to be a major mechanism contributing to epithelial barrier dysfunction in patients with compensated cirrhosis.
authors.affiliation: Division Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center, the Netherlands; School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University Medical Center, the Netherlands.
authors.forename: Kirsten E
authors.initials: KE
authors.lastname: Pijls
authors.affiliation: Division Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center, the Netherlands; School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University Medical Center, the Netherlands.
authors.forename: Daisy M A E
authors.initials: DM
authors.lastname: Jonkers
authors.affiliation: Division Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center, the Netherlands; School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University Medical Center, the Netherlands.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Elizalde
authors.affiliation: Department of Toxicology, Maastricht University Medical Center, the Netherlands; School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University Medical Center, the Netherlands.
authors.forename: Marie-Jose
authors.initials: MJ
authors.lastname: Drittij-Reijnders
authors.affiliation: Department of Toxicology, Maastricht University Medical Center, the Netherlands; School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University Medical Center, the Netherlands.
authors.forename: Guido R
authors.initials: GR
authors.lastname: Haenen
authors.affiliation: Department of Toxicology, Maastricht University Medical Center, the Netherlands; School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University Medical Center, the Netherlands.
authors.forename: Aalt
authors.initials: A
authors.lastname: Bast
authors.affiliation: Division Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center, the Netherlands; School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University Medical Center, the Netherlands.
authors.forename: Ad A M
authors.initials: AA
authors.lastname: Masclee
authors.affiliation: Division Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center, the Netherlands; School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University Medical Center, the Netherlands.
authors.forename: Ger H
authors.initials: GH
authors.lastname: Koek
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D016022:Case-Control Studies; D012809:Colon, Sigmoid / Q000737:chemistry*; D004386:Duodenum / Q000737:chemistry*; D005243:Feces / Q000737:chemistry; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D005978:Glutathione / Q000032:analysis; D019803:Glutathione Disulfide / Q000032:analysis; D005980:Glutathione Reductase / Q000235:genetics; D005981:Glutathione Synthase / Q000235:genetics; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry*; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics; D009195:Peroxidase / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: D015415:Biomarkers; D039841:Leukocyte L1 Antigen Complex; D009195:Peroxidase; D005980:Glutathione Reductase; D005981:Glutathione Synthase; D005978:Glutathione; D019803:Glutathione Disulfide