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Pentoxifylline improves liver regeneration through down-regulation of TNF-α synthesis and TGF-β1 gene expression
Rodrigo Bronze Martino1, Ana Maria Mendonça Coelho, Márcia Saldanha Kubrusly
1Rodrigo 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.
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.
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