Beneficial effects of adenosine triphosphate-sensitive K+ channel opener on liver ischemia/reperfusion injury.

Autor:	Nogueira MA; Mateus Antunes Nogueira, Ana Maria Mendonça Coelho, Sandra Nassa Sampietre, Rosely Antunes Patzina, Fabiano Pinheiro da Silva, Luiz Augusto Carneiro D'Albuquerque, Marcel Cerqueira Cesar Machado, Department of Gastroenterology (LIM/37), Medical School, University of Sao Paulo, Sao Paulo 01246903, Brazil., Coelho AM; Mateus Antunes Nogueira, Ana Maria Mendonça Coelho, Sandra Nassa Sampietre, Rosely Antunes Patzina, Fabiano Pinheiro da Silva, Luiz Augusto Carneiro D'Albuquerque, Marcel Cerqueira Cesar Machado, Department of Gastroenterology (LIM/37), Medical School, University of Sao Paulo, Sao Paulo 01246903, Brazil., Sampietre SN; Mateus Antunes Nogueira, Ana Maria Mendonça Coelho, Sandra Nassa Sampietre, Rosely Antunes Patzina, Fabiano Pinheiro da Silva, Luiz Augusto Carneiro D'Albuquerque, Marcel Cerqueira Cesar Machado, Department of Gastroenterology (LIM/37), Medical School, University of Sao Paulo, Sao Paulo 01246903, Brazil., Patzina RA; Mateus Antunes Nogueira, Ana Maria Mendonça Coelho, Sandra Nassa Sampietre, Rosely Antunes Patzina, Fabiano Pinheiro da Silva, Luiz Augusto Carneiro D'Albuquerque, Marcel Cerqueira Cesar Machado, Department of Gastroenterology (LIM/37), Medical School, University of Sao Paulo, Sao Paulo 01246903, Brazil., Pinheiro da Silva F; Mateus Antunes Nogueira, Ana Maria Mendonça Coelho, Sandra Nassa Sampietre, Rosely Antunes Patzina, Fabiano Pinheiro da Silva, Luiz Augusto Carneiro D'Albuquerque, Marcel Cerqueira Cesar Machado, Department of Gastroenterology (LIM/37), Medical School, University of Sao Paulo, Sao Paulo 01246903, Brazil., D'Albuquerque LA; Mateus Antunes Nogueira, Ana Maria Mendonça Coelho, Sandra Nassa Sampietre, Rosely Antunes Patzina, Fabiano Pinheiro da Silva, Luiz Augusto Carneiro D'Albuquerque, Marcel Cerqueira Cesar Machado, Department of Gastroenterology (LIM/37), Medical School, University of Sao Paulo, Sao Paulo 01246903, Brazil., Machado MC; Mateus Antunes Nogueira, Ana Maria Mendonça Coelho, Sandra Nassa Sampietre, Rosely Antunes Patzina, Fabiano Pinheiro da Silva, Luiz Augusto Carneiro D'Albuquerque, Marcel Cerqueira Cesar Machado, Department of Gastroenterology (LIM/37), Medical School, University of Sao Paulo, Sao Paulo 01246903, Brazil.
Jazyk:	angličtina
Zdroj:	World journal of gastroenterology [World J Gastroenterol] 2014 Nov 07; Vol. 20 (41), pp. 15319-26.
DOI:	10.3748/wjg.v20.i41.15319
Abstrakt:	Aim: To investigate the effect of diazoxide administration on liver ischemia/reperfusion injury. Methods: Wistar male rats underwent partial liver ischemia performed by clamping the pedicle from the medium and left anterior lateral segments for 1 h under mechanical ventilation. They were divided into 3 groups: Control Group, rats submitted to liver manipulation, Saline Group, rats received saline, and Diazoxide Group, rats received intravenous injection diazoxide (3.5 mg/kg) 15 min before liver reperfusion. 4 h and 24 h after reperfusion, blood was collected for determination of aspartate transaminase (AST), alanine transaminase (ALT), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), nitrite/nitrate, creatinine and tumor growth factor-β1 (TGF-β1). Liver tissues were assembled for mitochondrial oxidation and phosphorylation, malondialdehyde (MDA) content, and histologic analysis. Pulmonary vascular permeability and myeloperoxidase (MPO) were also determined. Results: Four hours after reperfusion the diazoxide group presented with significant reduction of AST (2009 ± 257 U/L vs 3523 ± 424 U/L, P = 0.005); ALT (1794 ± 295 U/L vs 3316 ± 413 U/L, P = 0.005); TNF-α (17 ± 9 pg/mL vs 152 ± 43 pg/mL, P = 0.013; IL-6 (62 ± 18 pg/mL vs 281 ± 92 pg/mL); IL-10 (40 ± 9 pg/mL vs 78 ± 10 pg/mL P = 0.03), and nitrite/nitrate (3.8 ± 0.9 μmol/L vs 10.2 ± 2.4 μmol/L, P = 0.025) when compared to the saline group. A significant reduction in liver mitochondrial dysfunction was observed in the diazoxide group compared to the saline group (P < 0.05). No differences in liver MDA content, serum creatinine, pulmonary vascular permeability and MPO activity were observed between groups. Twenty four hours after reperfusion the diazoxide group showed a reduction of AST (495 ± 78 U/L vs 978 ± 192 U/L, P = 0.032); ALT (335 ± 59 U/L vs 742 ± 182 U/L, P = 0.048), and TGF-β1 (11 ± 1 ng/mL vs 17 ± 0.5 ng/mL, P = 0.004) serum levels when compared to the saline group. The control group did not present alterations when compared to the diazoxide and saline groups. Conclusion: Diazoxide maintains liver mitochondrial function, increases liver tolerance to ischemia/reperfusion injury, and reduces the systemic inflammatory response. These effects require further evaluation for using in a clinical setting.
Databáze:	MEDLINE
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