title: Effects of the administration of pentoxifylline and prednisolone on the evolution of portal fibrogenesis secondary to biliary obstruction in growing animals: immunohistochemical analysis of the expression of TGF-β and VEGF.
abstract: OBJECTIVE
  During the neonatal and infancy periods, some chronic liver diseases may lead to progressive hepatic fibrosis, which is a condition that can ultimately result in the loss of organ function and severe portal hypertension necessitating hepatic transplantation. In a previous report, pharmacological interventions were demonstrated to modulate hepatic fibrosis induced by bile duct ligation in young rats. The administration of pentoxifylline or prednisolone, or the combination of both, resulted in reduced fibrogenesis in portal spaces. The objectives of the present study were to evaluate the expression of transforming growth factor β and vascular endothelial growth factor after bile duct ligation in young rats and to assess the effect of those same drugs on cytokine expression.
  
  
  METHODS
  In this experimental study, 80 young rats (21 or 22 days old) were submitted either to laparotomy and common bile duct ligation or to sham surgery. The animals were allocated into four groups according to surgical procedure, and the following treatments were administered: (1) common bile duct ligation + distilled water, (2) sham surgery + distilled water, (3) common bile duct ligation + pentoxifylline, or (4) common bile duct ligation + prednisolone. After 30 days, a hepatic fragment was collected from each animal for immunohistochemical analysis using monoclonal antibodies against transforming growth factor β and vascular endothelial growth factor. Digital morphometric and statistical analyses were performed.
  
  
  RESULTS
  The administration of pentoxifylline reduced the transforming growth factor β-marked area and the amount of transforming growth factor β expressed in liver tissue. This effect was not observed after the administration of prednisolone. There was a significant reduction in vascular endothelial growth factor expression after the administration of either drug compared with the non-treatment group.
  
  
  CONCLUSIONS
  The administration of pentoxifylline to cholestatic young rats resulted in the diminished expression of transforming growth factor β and vascular endothelial growth factor in liver tissue. The administration of steroids resulted in the diminished expression of vascular endothelial growth factor only. These pathways may be involved in hepatic fibrogenesis in young rats submitted to bile duct ligation and exposed to pentoxifylline or prednisolone.
authors.affiliation: Faculdade de Medicina da Universidade de São Paulo, Pediatric Surgery Division, Laboratory of Pediatric Surgery (LIM-30) and Laboratory of Hepatic Pathology (LIM-14), São Paulo/SP, Brazil. wwwag@uol.com.br
authors.forename: Wagner de Castro
authors.initials: Wde C
authors.lastname: Andrade
authors.forename: Luiz Fernando Ferraz da
authors.initials: LF
authors.lastname: Silva
authors.forename: Maria Cecilia de Mendonça
authors.initials: MC
authors.lastname: Coelho
authors.forename: Ana Cristina Aoun
authors.initials: AC
authors.lastname: Tannuri
authors.forename: Venancio Avancini Ferreira
authors.initials: VA
authors.lastname: Alves
authors.forename: Uenis
authors.initials: U
authors.lastname: Tannuri
mesh_terms: D000818:Animals; D002779:Cholestasis / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000494:pharmacology*; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D010431:Pentoxifylline / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011239:Prednisolone / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D010726:Phosphodiesterase Inhibitors; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D011239:Prednisolone; D010431:Pentoxifylline