Open AccessProtective effect of apelin preconditioning in a rat model of hepatic ischemia reperfusion injury; possible interaction between the apelin/APJ system, Ang II/AT1R system and eNOS
Author(s) -
Sabry Maha M,
Ramadan Nagwa M,
Al Dreny Basant A,
Rashed Laila A,
Abo El Enein Ayman
Publication year - 2019
Publication title -
ueg journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.667
H-Index - 35
eISSN - 2050-6414
pISSN - 2050-6406
DOI - 10.1177/2050640619826847
Subject(s) - apelin , medicine , malondialdehyde , nitric oxide synthase , reperfusion injury , enos , angiotensin ii , nitric oxide , endocrinology , endothelial nos , pharmacology , ischemia , receptor , oxidative stress
Hepatic ischemic reperfusion injury occurs in multiple clinical settings. Novel potential protective agents are still needed to attenuate this injury. Apelin preconditioning protects against ischemic reperfusion injury in different organs. However, the protective mechanism of apelin on hepatic ischemic reperfusion injury is not yet clear. Aim Evaluate the effect of apelin‐13 preconditioning on hepatic ischemic reperfusion injury and clarify possible interactions between apelinergic, renin‐angiotensin systems and endothelial nitric oxide synthase. Methods In total, 60 rats were assigned to four groups: control sham‐operated, ischemic reperfusion, apelin‐treated ischemic reperfusion and apelin + N‐nitro‐L‐arginine methyl ester‐treated ischemic reperfusion. Apelin 2 µg/kg/day and N‐nitro‐L‐arginine methyl ester 10 mg/kg/day were injected intraperitoneally daily for 3 days and 2 weeks respectively before hepatic ischemic reperfusion. Serum aminotransferase, aspartate aminotransferase, hepatic malondialdehyde, apelin, gene expression of caspase‐3, endothelial nitric oxide synthase and angiotensin type 1 receptor and liver histopathology were compared between groups. Results Apelin significantly reduced serum aminotransferase, aspartate aminotransferase, hepatic malondialdehyde, caspase‐3 and angiotensin type 1 receptor expression, whereas hepatic apelin and endothelial nitric oxide synthase expression were significantly increased with improved hepatic histopathology. N‐nitro‐L‐arginine methyl ester co‐administration partially reversed this hepatoprotective effect. Conclusion Apelin‐13 reduced hepatic ischemic reperfusion injury. This protection could be related to the suppression of hepatic angiotensin type 1 receptor expression and elevation of hepatic apelin level and endothelial nitric oxide synthase expression, which counteracts the pathologic effects of Ang II/angiotensin type 1 receptor. An interaction exists between apelinergic, renin‐angiotensin systems and endothelial nitric oxide synthase in hepatic ischemic reperfusion pathophysiology.