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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
Andrade, Wagner de Castro; Silva, Luiz Fernando Ferraz da; Coelho, Maria Cecilia de Mendonça; Tannuri, Ana Cristina Aoun; Alves, Venancio Avancini Ferreira; Tannuri, Uenis.
  • Andrade, Wagner de Castro; Universidade de São Paulo. Faculdade de Medicina. Pediatric Surgery Division. , Laboratory of Pediatric Surgery Laboratory of Hepatic Pathology. São Paulo. BR
  • Silva, Luiz Fernando Ferraz da; Universidade de São Paulo. Faculdade de Medicina. Pediatric Surgery Division. , Laboratory of Pediatric Surgery Laboratory of Hepatic Pathology. São Paulo. BR
  • Coelho, Maria Cecilia de Mendonça; Universidade de São Paulo. Faculdade de Medicina. Pediatric Surgery Division. , Laboratory of Pediatric Surgery Laboratory of Hepatic Pathology. São Paulo. BR
  • Tannuri, Ana Cristina Aoun; Universidade de São Paulo. Faculdade de Medicina. Pediatric Surgery Division. , Laboratory of Pediatric Surgery Laboratory of Hepatic Pathology. São Paulo. BR
  • Alves, Venancio Avancini Ferreira; Universidade de São Paulo. Faculdade de Medicina. Pediatric Surgery Division. , Laboratory of Pediatric Surgery Laboratory of Hepatic Pathology. São Paulo. BR
  • Tannuri, Uenis; Universidade de São Paulo. Faculdade de Medicina. Pediatric Surgery Division. , Laboratory of Pediatric Surgery Laboratory of Hepatic Pathology. São Paulo. BR
Clinics ; 67(12): 1455-1461, Dec. 2012. ilus
Article in English | LILACS | ID: lil-660475
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.
Subject(s)


Full text: Available Index: LILACS (Americas) Main subject: Pentoxifylline / Phosphodiesterase Inhibitors / Prednisolone / Cholestasis / Transforming Growth Factor beta / Vascular Endothelial Growth Factor A / Glucocorticoids / Liver Cirrhosis, Experimental Type of study: Etiology study / Prognostic study Limits: Animals Language: English Journal: Clinics Journal subject: Medicine Year: 2012 Type: Article / Project document Affiliation country: Brazil Institution/Affiliation country: Universidade de São Paulo/BR

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Full text: Available Index: LILACS (Americas) Main subject: Pentoxifylline / Phosphodiesterase Inhibitors / Prednisolone / Cholestasis / Transforming Growth Factor beta / Vascular Endothelial Growth Factor A / Glucocorticoids / Liver Cirrhosis, Experimental Type of study: Etiology study / Prognostic study Limits: Animals Language: English Journal: Clinics Journal subject: Medicine Year: 2012 Type: Article / Project document Affiliation country: Brazil Institution/Affiliation country: Universidade de São Paulo/BR