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

Author(s)

Nogueira, Mateus Antunes ^{[1, 2]} ; Mendonca Coelho, Ana Maria ^{[1, 2]} ; Sampietre, Sandra Nassa ^{[1, 2]} ; Patzina, Rosely Antunes ^{[1, 2]} ; da Silva, Fabiano Pinheiro ^{[1, 2]} ; Carneiro D'Albuquerque, Luiz Augusto ^{[1, 2]} ; Cesar Machado, Marcel Cerqueira ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Sch Med, Dept Gastroenterol LIM 37, BR-01246903 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Dept Clin Emergency LIM 51, BR-01246903 Sao Paulo - Brazil

• Document type: Journal article
• Source: WORLD JOURNAL OF GASTROENTEROLOGY; v. 20, n. 41, p. 15319-15326, NOV 7 2014.
• Web of Science Citations: 10

Abstract

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-alpha), interleukin-6 (IL-6), interleukin-10 (IL-10), nitrite/nitrate, creatinine and tumor growth factor-beta 1 (TGF-beta 1). 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-alpha (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 mu mol/L vs 10.2 +/- 2.4 mu mol/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-beta 1 (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. (C) 2014 Baishideng Publishing Group Inc. All rights reserved. (AU)

• FAPESP's process: 10/19078-1 - Effect of diazoxide on liver ischemia/reperfusion lesions: experimental study in rats
• Grantee: Marcel Cerqueira Cesar Machado
• Support Opportunities: Regular Research Grants