| 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 |
Abstract
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)