Hana Nasrallah1, Imen Aissa2, Chérifa Slim1, Mohamed Ali Boujbiha3, Mohamed Amine Zaouali4, Mohamed Bejaoui1, Victoria Wilke1, Hichem Ben Jannet2, Habib Mosbah3, Hassen Ben Abdennebi1. 1. Laboratoire de Génome Humain et Maladies Multifactorielles (LR12ES07), Faculté de Pharmacie de Monastir, Université de Monastir, Tunisia. 2. Laboratoire de Chimie Hétérocyclique, Produits Naturels et Réactivité, équipe: Chimie Médicinale et Produits Naturels (LR11ES39), Faculté des Sciences de Monastir, Université de Monastir, Monastir, Tunisia. 3. Laboratoire de Bioressources: Biologie Intégrative & Valorisation (LR14ES06), Institut Supérieur de Biotechnologie de Monastir, Université de Monastir, Monastir, Tunisia. 4. Laboratoire de Génome Humain et Maladies Multifactorielles (LR12ES07), Faculté de Pharmacie de Monastir, Université de Monastir, Tunisia; Département des Sciences du Vivant et Biotechnologie, Institut Supérieur de Biotechnologie de Monastir, Université de Monastir, Monastir, Tunisia. Electronic address: daminzaouali12@yahoo.fr.
Abstract
AIMS: This study aimed to evaluate the effect of oleuropein (OLE), the main phenolic compound present in olive leaves, on kidney ischemia-reperfusion injury (IRI) and to explore the underlying protective mechanism. MAIN METHODS: Rat kidneys were subjected to 60 min of bilateral warm ischemia followed by 120 min of reperfusion. OLE was administered orally 48 h, 24 h and 30 min prior to ischemia at doses of 10, 50 and 100 mg/kg body weight. The creatinine, urea, uric acid concentrations and lactate dehydrogenase (LDH) activity in plasma were evaluated. Oxidative stress and inflammation parameters were also assessed. Renal expression of AMP-activated protein kinase (p-AMPK), endothelial nitric oxide synthase (eNOS), mitogen-activated protein kinases (MAPK), inflammatory proteins and apoptotic proteins were evaluated using Western blot. KEY FINDINGS: Our results showed that OLE at 50 mg/kg reduced kidney IRI as revealed by a significant decrease of plasmatic creatinine, urea, uric acid concentrations and LDH activity. In parallel, OLE up-regulated antioxidant capacities. Moreover, OLE diminished the level of CRP and the expression of cyclooxygenase 2 (COX-2). Finally, OLE enhanced AMPK phosphorylation as well as eNOS expression whereas MAPK, and cleaved caspase-3 implicated in cellular apoptosis were attenuated in the ischemic kidneys. SIGNIFICANCE: In conclusion, this study shows that OLE could be used as therapeutic agent to reduce IRI through its anti-oxidative, anti-inflammatory and anti-apoptotic properties.
AIMS: This study aimed to evaluate the effect of oleuropein (OLE), the main phenolic compound present in olive leaves, on kidney ischemia-reperfusion injury (IRI) and to explore the underlying protective mechanism. MAIN METHODS:Rat kidneys were subjected to 60 min of bilateral warm ischemia followed by 120 min of reperfusion. OLE was administered orally 48 h, 24 h and 30 min prior to ischemia at doses of 10, 50 and 100 mg/kg body weight. The creatinine, urea, uric acid concentrations and lactate dehydrogenase (LDH) activity in plasma were evaluated. Oxidative stress and inflammation parameters were also assessed. Renal expression of AMP-activated protein kinase (p-AMPK), endothelial nitric oxide synthase (eNOS), mitogen-activated protein kinases (MAPK), inflammatory proteins and apoptotic proteins were evaluated using Western blot. KEY FINDINGS: Our results showed that OLE at 50 mg/kg reduced kidney IRI as revealed by a significant decrease of plasmatic creatinine, urea, uric acid concentrations and LDH activity. In parallel, OLE up-regulated antioxidant capacities. Moreover, OLE diminished the level of CRP and the expression of cyclooxygenase 2 (COX-2). Finally, OLE enhanced AMPK phosphorylation as well as eNOS expression whereas MAPK, and cleaved caspase-3 implicated in cellular apoptosis were attenuated in the ischemic kidneys. SIGNIFICANCE: In conclusion, this study shows that OLE could be used as therapeutic agent to reduce IRI through its anti-oxidative, anti-inflammatory and anti-apoptotic properties.