title: Evidence for intestinal oxidative stress in obstructive jaundice-induced gut barrier dysfunction in rats.
abstract: OBJECTIVE
  An important factor that promotes bacterial and endotoxin translocation in obstructive jaundice is intestinal injury that causes increased permeability. However, little is known of the submicroscopic biochemical events leading to defects of the intestinal barrier. This study was undertaken to investigate the effect of experimental obstructive jaundice on intestinal lipid peroxidation, protein oxidation and thiol redox state.
  
  
  METHODS
  Rats were randomly divided into controls, sham operated and bile duct ligated (BDL). After 10 days, intestinal barrier function was assessed by measuring endotoxin in portal and aortic blood. Tissue samples from the terminal ileum were examined histologically and morphometrically, while other samples were homogenized for the determination of lipid peroxidation, protein oxidation and thiol redox state [reduced glutathione (GSH), oxidized glutathione (GSSG), total non-protein mixed disulphides (NPSSR), protein thiols (PSH) and protein disulphides (PSSP)].
  
  
  RESULTS
  Obstructive jaundice compromised intestinal barrier function leading to significant portal and systemic endotoxaemia. The intestinal mucosa in jaundiced rats was atrophic with significantly decreased villous density and total mucosal thickness. Determination of biochemical parameters of oxidative stress in the intestine showed increased lipid peroxidation and protein oxidation in BDL-rats. Thiol redox state revealed the presence of intestinal oxidative stress in jaundiced rats, indicated by a decrease in GSH and increased GSSG, NPSSR and PSSP.
  
  
  CONCLUSIONS
  This study shows that experimental obstructive jaundice induces intestinal oxidative stress, which may be a key factor contributing to intestinal injury and leading to endotoxin translocation.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, School of Medicine, University of Patras, Patras, Greece.
authors.forename: S F
authors.initials: SF
authors.lastname: Assimakopoulos
authors.forename: C E
authors.initials: CE
authors.lastname: Vagianos
authors.forename: N
authors.initials: N
authors.lastname: Patsoukis
authors.forename: C
authors.initials: C
authors.lastname: Georgiou
authors.forename: V
authors.initials: V
authors.lastname: Nikolopoulou
authors.forename: C D
authors.initials: CD
authors.lastname: Scopa
mesh_terms: D000818:Animals; D001663:Bilirubin / Q000097:blood; D002432:Cecum / Q000382:microbiology; D004731:Endotoxins / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D007413:Intestinal Mucosa / Q000473:pathology / Q000502:physiology; D007422:Intestines / Q000473:pathology / Q000502:physiology*; D041781:Jaundice, Obstructive / Q000473:pathology / Q000503:physiopathology*; D015227:Lipid Peroxidation / Q000502:physiology*; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D011506:Proteins / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000378:metabolism*
chemical_list: D004731:Endotoxins; D011506:Proteins; D013438:Sulfhydryl Compounds; D005978:Glutathione; D001663:Bilirubin