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Background/Aim: Pretreatment with diazoxide, an opening mitoKATP, increases tissue tolerance against ischemia/reperfusion (I/R) injury, however, there are no prior studies of the role of diazoxide on hepatic I/R injury. In the present study, we evaluated the effect of diazoxide on local and systemic liver I/R process.
Methods: Wistar male rats underwent partial liver ischemia performed by clamping the pedicle from medium and left anterior lateral segments during an hour under mechanical ventilation. They were divided into 2 groups: Control Group (n=26): rats received saline and Diazoxide Group (n=26): rats received IV diazoxide (3.5mg/kg) 15 minutes before liver reperfusion. Four and 24 hours after reperfusion, blood were collected for determinations of AST, ALT, TNF-α, IL-6, IL-10, and TGFβ1. Liver tissues were assembled for mitochondrial oxidation and phosphorylation, malondialdehyde (MDA) content, and histologic analysis. Pulmonary vascular permeability and myeloperoxidade (MPO) were also determined.
Results: Four hours after reperfusion Diazoxide Group presented elevation of AST, ALT, TNF-α, IL-6, IL-10 and TGFβ1 serum levels significantly lower than Control Group (p<0.05). A significant reduction on liver MDA content and on mitochondrial dysfunction were observed in Diazoxide Group compared to Control Group (p<0.05). No differences in pulmonary vascular permeability and MPO activity were observed between groups. Twenty four hours after reperfusion Diazoxide Group showed a reduction of AST, ALT, and TGFβ1 serum levels when compared to Control group (p<0.05).
Conclusion: Diazoxide maintains liver mitochondrial function, increases liver tolerance to I/R injury, and reduces systemic inflammatory response. These effects require further evaluations for using in a clinical setting.
Grants from FAPESP2010/19078-1