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The effect of zinc acexamate on oxidative stress, inflammation and mitochondria induced apoptosis in rat model of renal warm ischemia

AutorHadj-Abdallah, Najet; Baulies, Anna ; Bouhlel, Ahlem; Bejaoui, Mohamed ; Zaouali, Mohamed A. ; Ben Mimouna, Safa; Messaoudi, Imed; Fernández-Checa, José C. ; García-Ruiz, Carmen ; Abdennebi, Hassen B.
Palabras claveZinc acexamate
Ischemia reperfusion injury
Oxidative stress
Fecha de publicaciónsep-2018
CitaciónBiomedicine and Pharmacotherapy 105: 573-581 (2018)
ResumenAim: 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 inducedapoptosis. 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.
Versión del editorhttps://doi.org/10.1016/j.biopha.2018.06.017
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