Altered occludin expression in brain capillaries induced by obstructive jaundice in rats

The development of increased oxidative stress in the context of obstructive cholestasis has been proven in various rats' organs including the brain. The present study aimed to detect alterations of tight junction-associated occludin in rat brain capillaries after bile duct ligation (BDL). In experiment 1, occludin expression was evaluated by Western blot analysis in 5 animals 10 days after BDL and compared with 5 sham-operated ones. In experiment 2, groups of 9 animals each were used to assess occludin levels on the 1st, 5th, and 10th days after BDL and to associate these measurements with the in vivo superoxide radical production measured by means of an ultrasensitive fluorescent assay. The results indicated that occludin expression in BDL animals, as opposed to sham-operated, was significantly reduced at every time point studied, being lowest in the rats remaining on BDL condition for 10 days. Moreover, it was demonstrated that the time-dependent downregulation of occludin expression in the brain endothelial was significantly correlated with the time-dependent increase of brain superoxide radical level, implying a relationship between these two abnormalities. In conclusion, the evidence presented herein suggests the implication of occludin and, therefore, of blood-brain barrier in the pathophysiology of extrahepatic cholestasis. (C) 2010 Elsevier B.V. All rights reserved.