Najet Hadj Abdallah1, Anna Baulies2, Ahlem Bouhlel3, Mohamed Bejaoui4, Mohamed Amine Zaouali5, Safa Ben Mimouna6, Imed Messaoudi7, José Carlos Fernandez-Checa8, Carmen García Ruiz9, Hassen Ben Abdennebi10. 1. Department of physiology, Unité de Biologie et anthropologie moléculaires appliquées au développement et à la santé, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia. Electronic address: nejet_hadjabd@hotmail.fr. 2. Department of Cell Death and Proliferation, Instituto de Investigaciones Biomédicas de Barcelona, Consejo Superior de Investigaciones Científicas. Liver Unit Hospital Clínici Provincial, IDIBAPS and CIBERehd, 08036, Barcelona, Spain. Electronic address: abaulies@gmail.com. 3. Department of physiology, Unité de Biologie et anthropologie moléculaires appliquées au développement et à la santé, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia. Electronic address: ah.lemk@live.fr. 4. Department of physiology, Unité de Biologie et anthropologie moléculaires appliquées au développement et à la santé, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia. Electronic address: bjaouiph@hotmail.fr. 5. Department of physiology, Unité de Biologie et anthropologie moléculaires appliquées au développement et à la santé, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia. Electronic address: daminzaouali12@yahoo.fr. 6. Laboratoire de Génétique, Biodiversité et Valorisation des Bioressources (LR11ES41). Institute of Biotechnology, University of Monastir, Monastir, Tunisia. Electronic address: benmimounasafa@yahoo.fr. 7. Laboratoire de Génétique, Biodiversité et Valorisation des Bioressources (LR11ES41). Institute of Biotechnology, University of Monastir, Monastir, Tunisia. Electronic address: imed_messaoudi@yahoo.fr. 8. Department of Cell Death and Proliferation, Instituto de Investigaciones Biomédicas de Barcelona, Consejo Superior de Investigaciones Científicas. Liver Unit Hospital Clínici Provincial, IDIBAPS and CIBERehd, 08036, Barcelona, Spain. Electronic address: checa229@yahoo.com. 9. Department of Cell Death and Proliferation, Instituto de Investigaciones Biomédicas de Barcelona, Consejo Superior de Investigaciones Científicas. Liver Unit Hospital Clínici Provincial, IDIBAPS and CIBERehd, 08036, Barcelona, Spain. Electronic address: carmen.garcia@iibb.csic.es. 10. Department of physiology, Unité de Biologie et anthropologie moléculaires appliquées au développement et à la santé, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia. Electronic address: hbenabdennebi@yahoo.fr.
Abstract
AIM: Zinc has proved its efficacy in many models of ischemia reperfusion (I/R) injury. In this study, we used zinc acexamate (ZAC) as an exogenous source of zinc against renal I/R injury and we investigated whether its protective effects are mediated by the decrease of oxidative stress, inflammation, and mitochondria induced-apoptosis. METHODS: Rats were orally pretreated with vehicle or ZAC (10 or 100 mg/kg) 24 h and 30 min prior to 1 h of bilateral renal warm ischemia and 2 h of reperfusion. RESULTS: Our data showed that 10 mg/kg of ZAC, but not 100 mg/kg, improved renal architecture and function. Also, the low dose of ZAC up-regulated antioxidant enzymes activities and glutathione level and decreased lipids and proteins oxidation. Interestingly, the use of ZAC resulted in a significant reduce of pro-inflammatory cytokines (IL-1ß, IL-6 and MCP-1), enhanced mitochondria integrity and decreased expression of the pro-apoptotic protein caspase-9. CONCLUSION: We conclude that renal I/R induced oxidative stress, inflammation and apoptosis and that the use of ZAC at 10 mg/kg, but not 100 mg/kg, protects rat kidneys from I/R injury by down-regulating these processes.
AIM: Zinc has proved its efficacy in many models of ischemia reperfusion (I/R) injury. In this study, we used zinc acexamate (ZAC) as an exogenous source of zinc against renal I/R injury and we investigated whether its protective effects are mediated by the decrease of oxidative stress, inflammation, and mitochondria induced-apoptosis. METHODS:Rats were orally pretreated with vehicle or ZAC (10 or 100 mg/kg) 24 h and 30 min prior to 1 h of bilateral renal warm ischemia and 2 h of reperfusion. RESULTS: Our data showed that 10 mg/kg of ZAC, but not 100 mg/kg, improved renal architecture and function. Also, the low dose of ZAC up-regulated antioxidant enzymes activities and glutathione level and decreased lipids and proteins oxidation. Interestingly, the use of ZAC resulted in a significant reduce of pro-inflammatory cytokines (IL-1ß, IL-6 and MCP-1), enhanced mitochondria integrity and decreased expression of the pro-apoptotic protein caspase-9. CONCLUSION: We conclude that renal I/R induced oxidative stress, inflammation and apoptosis and that the use of ZAC at 10 mg/kg, but not 100 mg/kg, protects rat kidneys from I/R injury by down-regulating these processes.