Protective effect of astaxanthin against contrast-induced acute kidney injury via SIRT1-p53 pathway in rats
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The present study was designed to further investigate the protective effect of astaxanthin (AST) on contrast-induced acute kidney injury (CI-AKI) in rats and the relationship between SIRT1-p53 pathway and astaxanthin.
40 adult male Sprague Dawley (SD) rats were randomly divided into five groups (n = 8/group): control (CON), normal rats treated with AST (AST), CM-treated (CM), CM rats treated with isoform of nitric oxide synthase (iNOS) inhibitor (iNOS + CM), and CM rats treated with AST (AST + CM). Serum creatinine (Scr) and blood urea nitrogen (BUN) values were measured at 72 h following the procedure. Hematoxylin and eosin (H–E) staining was used to observe the pathologic changes of kidney. Tunel staining was used to test apoptosis of kidney tubules. Oxidative stress, SIRT1 activity, nitric oxide (NO), and 3-nitrotyrosine (3-NT) content were individually measured with the commercial available kits.
Compared with the CON group, Scr and BUN levels significantly increased in the CM group (P < 0.05), and the values in two pre-treatment groups (iNOS + CM and AST + CM) had significantly decreased (P < 0.05). H–E and Tunel staining had shown that renal tubular injury was severe in CM group. The renal injury score and apoptosis index in the two pre-treatment groups also decreased (P < 0.05). The present study showed that in CM group the levels of oxidative stress indicators significantly increased, and the activities of antioxidant stress indicators significantly decreased. These indicators in two pre-treatment groups significantly improved (P < 0.05). In the CM group the expression levels of SITR1 significantly increased, and the ac-p53/p53 significantly increased (P < 0.05). Compared with the CM group, in AST + CM group the expression levels of SIRT1 increased, the expression levels of p53 and ac-p53/p53 decreased (P < 0.05).The levels of NO and 3-NT in CM group significantly increased (P < 0.05). Compared the CM group, the levels in the two pre-treatment groups significantly decreased (P < 0.05).
Astaxanthin has a protective effect on CI-AKI, the mechanism may be related to the SIRT1-p53 pathway. Astaxanthin can reduce the content of NO and 3-NT in renal tissue of CI-AKI, and alleviate the renal injury induced by contrast agents.
KeywordsAcute kidney injury Astaxanthin Oxidative stress Apoptosis SIRT1-p53 pathway 3-NT
This study was supported by a grant from the Six Talent Peaks Project in Jiangsu Province (CN) (2014-YY-007).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interest.
Experiments were performed in accordance with the Guide for the Care and Use of Laboratory Animals published in P.R. China and with the approval of Xuzhou Medical University Ethics Committee.
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