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Abstract
Background: Apelin with its G-protein-coupled receptor APJ system and renin - angiotensin system (RAS) have opposing actions on ischemia/reperfusion (I/R) injury. Objective: The purpose of the present study is to evaluate the possible hepato-protective effect of apelin and losartan on hepatic I/R injury in rat model and to clarify the possible interaction between Apelin/APJ system, RAS system and endothelial nitric oxide synthase (eNOS) and its impact on progression of hepatic dysfunction. Methods: Ninety male albino rats were divided to six groups (n=15): control sham- operated group, hepatic I/R group, apelin +I/R group , apelin + (L-NAME) non selective endothelial nitric oxide synthase inhibitor + I/R group, losartan +I/R group and Losartan + (L-NAME) + I/R group. All hepatic I/R groups underwent 30 minutes of ischemia followed by 2 hours of reperfusion. Apelin was injected intraperitoneally daily (2 æg/kg/day) starting 3 days prior to surgical hepatic I/R procedure. Losartan was given orally by syringe (30 mg/kg / day) daily 2 weeks prior to surgical hepatic I/R procedure. L-NAME was injected intraperitoneally (10 mg/kg/day) daily 2 weeks prior to surgical hepatic I/R procedure. At the end of the 2 weeks immediately after hepatic I/R procedure, blood samples were taken for examining serum level of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In addition, hepatic tissue was excised for estimation of hepatic gene expression of caspase-3 (CASP-3), endothelial nitric oxide synthase (eNOS) and Ang II type 1 receptor (AT1R) and level of malondialdehyde (MDA) and apelin in hepatic tissue. Finally, the rest of liver tissues were prepared for histopathological examination