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World J Gastroenterol. Jul 28, 2008; 14(28): 4505-4511
Published online Jul 28, 2008. doi: 10.3748/wjg.14.4505
Development of hepatorenal syndrome in bile duct ligated rats
Regina M Pereira, Robson AS dos Santos, Eduardo A Oliveira, Virgínia HR Leite, Filipi LC Dias, Alysson S Rezende, Lincoln P Costa, Lucíola S Barcelos, Mauro M Teixeira, Ana Cristina Simões e Silva
Regina M Pereira, Departamento de Ciências Biológicas, Centro Universitário de Belo Horizonte-UNIBH, Av. Mário Werneck, Belo Horizonte, Minas Gerais 30150-281, Brazil
Robson AS dos Santos, Laboratório de Hipertensão, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas (ICB), Universidade Federal de Minas Gerais (UFMG), Av. Antonio Carlos, 6627, Belo Horizonte, Minas Gerais 30150-281, Brazil
Eduardo A Oliveira, Filipi LC Dias, Alysson S Rezende, Lincoln P Costa, Ana Cristina Simões e Silva, Departamento de Pediatria, Faculdade de Medicina, UFMG, Av. Alfredo Balena 190, Belo Horizonte, Minas Gerais 30150-281, Brazil
Virgínia HR Leite, Departamento de Anatomia Patológica, Faculdade de Medicina, UFMG, Av. Alfredo Balena 190, Belo Horizonte, Minas Gerais 30150-281, Brazil
Lucíola S Barcelos, Mauro M Teixeira, Laboratório de Imunofarmacologia, Departamento de Bioquímica e Imunologia, ICB, UFMG, Av. Antonio Carlos 6627, Belo Horizonte, Minas Gerais 30150-281, Brazil
Author contributions: Simões e Silva AC, Pereira RM, dos Santos RAS and Teixeira MM designed research; Pereira RM, Leite VHR, Dias FLC, Rezende AS, Costa LP and Barcelos LS performed research; Simões e Silva AC, Pereira RM, Oliveira EA and Teixeira MM analyzed data; Simões e Silva AC, Teixeira MM, Pereira RM, Oliveira EA and dos Santos RAs wrote the paper.
Correspondence to: Ana Cristina Simões e Silva, MD, PhD, Departamento de Pediatria, Faculdade de Medicina, Endereço, Avenida Bernardo Monteiro, 1300 ap 1104, Funcionários, Belo Horizonte, Minas Gerais 30150-281, Brazil. acssilva@hotmail.com
Telephone: +55-31-30248687
Fax: +55-31-32489770
Received: March 28, 2008
Revised: June 5, 2008
Accepted: June 12, 2008
Published online: July 28, 2008
Abstract

AIM: To evaluate in bile duct ligated rats whether there were progressive alterations of renal function without changes in histopathology.

METHODS: Male Wistar rats were submitted to sham-surgery or bile duct ligation (BDL) and divided according to the post-procedure time (2, 4 and 6-wk). To determine renal function parameters, rats were placed in metabolic cages and, at the end of the experiment, blood and urine samples were obtained. Histology and hydroxyproline content were analyzed in liver and renal tissue.

RESULTS: Rats with 2 wk of BDL increased free water clearance (P = 0.02), reduced urinary osmolality (P = 0.03) and serum creatinine (P = 0.01) in comparison to the sham group. In contrast, rats at 6 wk of BDL showed features of HRS, including significant increase in serum creatinine and reductions in creatinine clearance, water excretion and urinary sodium concentration. Rats with 4 wk of BDL exhibited an intermediate stage of renal dysfunction. Progressive hepatic fibrosis according to post-procedure time was confirmed by histology. The increased levels of liver hydroxyproline contrasted with the absence of structural changes in the kidney, as assessed by histology and unchanged hydroxyproline content in renal tissue.

CONCLUSION: Our data show that BDL produced progressive renal dysfunction without structural changes in the kidney, characterizing HRS. The present model will be useful to understand the pathophysiology of HRS.

Keywords: Hepatorenal syndrome, Bile duct ligation, Renal function, Renin angiotensin system