The effect of zinc acexamate on oxidative stress, inflammation and mitochondria induced apoptosis in rat model of renal warm ischemia
[Display omitted] •Zinc acexamate preserves renal morphology and function after I/R.•Zinc acexamate prevents I/R-induced oxidative stress.•Zinc acexamate decreases the production of pro-inflammatory cytokines.•Zinc acexamate improves mitochondrial membrane integrity and decreases apoptosis. Zinc has...
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Published in | Biomedicine & pharmacotherapy Vol. 105; pp. 573 - 581 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
France
Elsevier Masson SAS
01.09.2018
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Subjects | |
Online Access | Get full text |
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Summary: | [Display omitted]
•Zinc acexamate preserves renal morphology and function after I/R.•Zinc acexamate prevents I/R-induced oxidative stress.•Zinc acexamate decreases the production of pro-inflammatory cytokines.•Zinc acexamate improves mitochondrial membrane integrity and decreases apoptosis.
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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0753-3322 1950-6007 |
DOI: | 10.1016/j.biopha.2018.06.017 |