Martino RB, Coelho AMM, Kubrusly MS, Leitão R, Sampietre SN, Machado MCC, Bacchella T, D’Albuquerque LAC. Pentoxifylline improves liver regeneration through down-regulation of TNF-α synthesis and TGF-β1 gene expression. World J Gastrointest Surg 2012; 4(6): 146-151 [PMID: 22816029 DOI: 10.4240/wjgs.v4.i6.146]
Corresponding Author of This Article
Marcel Cerqueira Cesar Machado, MD, Professor of Medicine, Department of Gastroenterology, University of Sao Paulo, AV. Dr. Arnaldo Viera de Carvalho, 455 - 3 andar, sala 3206,, Cerqueira Cesar, São Paulo 01246903, Brazil. amcoelho@usp.br
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World J Gastrointest Surg. Jun 27, 2012; 4(6): 146-151 Published online Jun 27, 2012. doi: 10.4240/wjgs.v4.i6.146
Pentoxifylline improves liver regeneration through down-regulation of TNF-α synthesis and TGF-β1 gene expression
Rodrigo Bronze Martino, Ana Maria Mendonça Coelho, Márcia Saldanha Kubrusly, Regina Leitão, Sandra Nassa Sampietre, Marcel Cerqueira Cesar Machado, Telesforo Bacchella, Luiz Augusto Carneiro D’Albuquerque
Rodrigo Bronze Martino, Ana Maria Mendonça Coelho, Márcia Saldanha Kubrusly, Regina Leitão, Sandra Nassa Sampietre, Marcel Cerqueira Cesar Machado, Telesforo Bacchella, Luiz Augusto Carneiro D’Albuquerque, Department of Gastroenterology (LIM/37), and Department of Surgery, Medical School, University of Sao Paulo, Sao Paulo 01246903, Brazil
Author contributions: Martino RB performed the research and analyzed the data; Coelho AMM performed the chemical analysis and wrote the paper; Kubrusly MS performed the molecular analysis; Leitão R performed the pathological analysis; Sampietre SN contributed to experimental procedures and collection of data; Machado MCC designed the research and wrote the paper; Bacchella T revised the manuscript; D’Albuquerque LAC provided materials and laboratory equipment and revised the manuscript.
Correspondence to: Marcel Cerqueira Cesar Machado, MD, Professor of Medicine, Department of Gastroenterology, University of Sao Paulo, AV. Dr. Arnaldo Viera de Carvalho, 455 - 3 andar, sala 3206,, Cerqueira Cesar, São Paulo 01246903, Brazil. amcoelho@usp.br
Telephone: +55-11-30618319 Fax: +55-11-30617270
Received: September 20, 2011 Revised: June 20, 2012 Accepted: June 23, 2012 Published online: June 27, 2012
Abstract
AIM: To investigate the mechanism of pentoxifylline (PTX) improvement in liver regeneration.
RESULTS: Rats were randomized into 4 groups: Control rats; Sham - sham-operation rats; Saline - 70% hepatectomy plus saline solution; PTX - 70% hepatectomy plus PTX. At 2 and 6 h after hepatectomy, aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) serum and hepatic tissue levels were determined. Tumor growth factor (TGF)-β1 gene expression in liver tissue was evaluated 24 h after hepatectomy by quantitative reverse transcriptase polymerase chain reaction analysis. Proliferation was analyzed by mitotic index and proliferating cell nuclear antigen (PCNA) staining 48 h after hepatectomy.
RESULTS: TNF-α and IL-6 serum levels increased at 2 and 6 h after hepatectomy. At 2 h after hepatectomy serum PTX was reduced but not hepatic levels of TNF-α and IL-6. A decrease in liver TGF-β1 gene expression and an increase in mitotic index and PCNA after hepatectomy were observed in the PTX treatment group in comparison to the saline group.
CONCLUSION: PTX improves liver regeneration by a mechanism related to down regulation of TNF-α production and TGF-β1 gene expression.