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Effect of diazoxide on liver ischemia/reperfusion lesions: experimental study in rats

Grant number: 10/19078-1
Support type:Regular Research Grants
Duration: March 01, 2011 - February 28, 2013
Field of knowledge:Health Sciences - Medicine - Surgery
Principal Investigator:Marcel Cerqueira Cesar Machado
Grantee:Marcel Cerqueira Cesar Machado
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Ana Maria de Mendonça Coelho


Previous studies have demonstrated that activation of mitochondrial ATP-sensitive potassium channels (mKATP) by diazoxide protects against ischemia/reperfusion injury in several organs, however there are no prior studies of the role of diazoxide on liver ischemic reperfusion injury. Liver ischemia/reperfusion (I/R) process can trigger a systemic inflammatory syndrome producing hepatic and remote organ damage that occurs in major liver resections and transplantation. In the present study we will evaluate the effect of diazoxide on local and systemic liver ischemia/reperfusion (I/R) process. Wistar male rats will be submitted partial liver ischemia by clamping the pedicle from medium and left anterior lateral segments during an hour under mechanical ventilation. They will be divided into 2 groups: Control Group: rats will receive saline and Diazoxide Group: rats will receive IV diazoxide (3.5mg/kg) 15 minutes before liver reperfusion. Four and 24 hours after reperfusion, blood will be collected for determinations of AST, ALT, TNF-alfa, TGF-beta, IL-6, IL-10, and nitrite/nitrate. Liver tissues will be assembled for histologic analysis, malondialdehyde (MDA) content, and mitochondrial oxidation and phosphorylation. Pulmonary vascular permeability and myeloperoxidade (MPO) also will be determined. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
NOGUEIRA, MATEUS ANTUNES; MENDONCA COELHO, ANA MARIA; SAMPIETRE, SANDRA NASSA; PATZINA, ROSELY ANTUNES; DA SILVA, FABIANO PINHEIRO; CARNEIRO D'ALBUQUERQUE, LUIZ AUGUSTO; CESAR MACHADO, MARCEL CERQUEIRA. Beneficial effects of adenosine triphosphate-sensitive K+ channel opener on liver ischemia/reperfusion injury. WORLD JOURNAL OF GASTROENTEROLOGY, v. 20, n. 41, p. 15319-15326, NOV 7 2014. Web of Science Citations: 10.

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