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-BETA; and VEGF

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art_ANDRADE_Effects_of_the_administration_of_pentoxifylline_and_prednisolone_2012.PDF (1.74 MB)
Citações na Scopus
7
Tipo de produção
article
Data de publicação
2012
DOI
SciELO
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
HOSPITAL CLINICAS, UNIV SAO PAULO
Autores
Citação
CLINICS, v.67, n.12, p.1455-1461, 2012
Projetos de Pesquisa
Unidades Organizacionais
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Resumo
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 beta 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 beta and vascular endothelial growth factor. Digital morphometric and statistical analyses were performed. RESULTS: The administration of pentoxifylline reduced the transforming growth factor beta-marked area and the amount of transforming growth factor beta 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 beta 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.
Palavras-chave
Liver Fibrogenesis, Experimental Cholestasis, Steroids, Pentoxifylline, TGF beta, VEGF
URI
https://observatorio.fm.usp.br/handle/OPI/994
Referências
  1. Andrade WD, 2009, J PEDIATR SURG, V44, P2071, DOI 10.1016/j.jpedsurg.2009.05.020
  2. Bender AT, 2006, PHARMACOL REV, V58, P488, DOI 10.1124/pr.58.3.5
  3. Carceller A, 2000, J PEDIATR SURG, V35, P717, DOI 10.1053/jpsu.2000.6034
  4. Conti M, 2007, ANNU REV BIOCHEM, V76, P481, DOI 10.1146/annurev.biochem.76.060305.150444
  5. Escobar MA, 2006, J PEDIATR SURG, V41, P99, DOI 10.1016/j.jpedsurg.2005.10.072
  6. Gaudio E, 2006, GASTROENTEROLOGY, V130, P1270, DOI 10.1053/j.gastro.2005.12.034
  7. Gibelli NEM, 2009, PEDIATR TRANSPLANT, V13, P81, DOI 10.1111/j.1399-3046.2008.00947.x
  8. Housset C, 2000, J HEPATOL, V32, P14, DOI 10.1016/S0168-8278(00)80436-5
  9. KARRER FM, 1985, J PEDIATR SURG, V20, P693, DOI 10.1016/S0022-3468(85)80026-9
  10. Kinnman N, 2002, FRONT BIOSCI, V7, pD496, DOI 10.2741/kinnman
  11. Kobayashi H, 2005, J PEDIATR SURG, V40, P327, DOI 10.1016/j.jpedsurg.2004.10.017
  12. Meyers RL, 2003, J PEDIATR SURG, V38, P406, DOI 10.1053/jpsu.2003.50069
  13. MINER PB, 1979, BIOCHEM PHARMACOL, V28, P1063, DOI 10.1016/0006-2952(79)90304-6
  14. Muraji T, 2004, J PEDIATR SURG, V39, P1803, DOI 10.1016/j.jpedsurg.2004.08.019
  15. Muraji T, 1997, J PEDIATR SURG, V32, P1103, DOI 10.1016/S0022-3468(97)90408-5
  16. Oberti F, 1997, J HEPATOL, V26, P1363, DOI 10.1016/S0168-8278(97)80473-4
  17. Omori K, 2007, CIRC RES, V100, P306
  18. Peterson TC, 1996, IMMUNOPHARMACOLOGY, V31, P183, DOI 10.1016/0162-3109(95)00048-8
  19. PETERSON TC, 1993, HEPATOLOGY, V17, P486, DOI 10.1016/0270-9139(93)90062-R
  20. Raetsch C, 2002, GUT, V50, P241, DOI 10.1136/gut.50.2.241
  21. Rhen T, 2005, NEW ENGL J MED, V353, P1711, DOI 10.1056/NEJMra050541
  22. Sarkhy A, 2011, CAN J GASTROENTEROL, V25, P440
  23. SCHANDENE L, 1992, IMMUNOLOGY, V76, P30
  24. Sokol RJ, 2001, SEMIN LIVER DIS, V21, P517, DOI 10.1055/s-2001-19032
  25. Stringer MD, 2007, J PEDIATR SURG, V42, P1324, DOI 10.1016/j.jpedsurg.2007.03.026
  26. Suzuki T, 2010, PEDIATR SURG INT, V26, P825, DOI 10.1007/s00383-010-2637-y
  27. Tarcin O, 2003, J GASTROEN HEPATOL, V18, P437, DOI 10.1046/j.1440-1746.2003.03004.x
  28. WARD A, 1987, DRUGS, V34, P50, DOI 10.2165/00003495-198734010-00003
  29. Windmeier C, 1997, GEN PHARMACOL, V29, P181, DOI 10.1016/S0306-3623(96)00314-X

Coleções
Artigos e Materiais de Revistas Científicas - FM/MPT
Artigos e Materiais de Revistas Científicas - FM/MCG
Artigos e Materiais de Revistas Científicas - FM/MPE
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - HC/ICr
Artigos e Materiais de Revistas Científicas - LIM/05
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