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International Urology and Nephrology

, Volume 50, Issue 6, pp 1171–1180 | Cite as

Astaxanthin attenuates contrast agent-induced acute kidney injury in vitro and in vivo via the regulation of SIRT1/FOXO3a expression

  • Nana Liu
  • Jing Chen
  • Dongmei Gao
  • Wenhua LiEmail author
  • Di Zheng
Nephrology - Original Paper

Abstract

Purpose

The study was processed to investigate the effect of astaxanthin (AST; 3,3-dihydroxybeta, beta-carotene-4,4-dione) on the acute kidney injury induced by iohexol and the relationship with SIRT1/FOXO3a signal pathway.

Methods

Thirty male Sprague Dawley rats were randomly divided into five groups as follows: control group (CON; olive oil only), contrast media group, astaxanthin control group (100 mg/kg), low astaxanthin dose group (LAG, 50 mg/kg) and high astaxanthin dose group (HAG, 100 mg/kg). As followed, serum creatinine (SCr), blood urea nitrogen (BUN), the oxidative stress markers and apoptosis-related proteins were detected. Human proximal tubular epithelial cells (HK-2) were cultured in DMEM/F12 medium in vitro and then randomly divided into appropriate experimental groups: normal group (N), dimethyl sulfoxide (DMSO), iohexol group (I), iohexol + (1.0, 10.0 μmol/L) astaxanthin group (I + LAST; I + HAST), iohexol + SIRT1 inhibitors (nicotinamide) group (NA) and iohexol + si-RNA FOXO3a group (si-RNA FOXO3a); when cultured for 24 h, cell proliferation ability was tested by cell counting kit (CCK-8), reactive oxygen species (ROS) were detected by flow cytometry and the expression of SIRT1 and FOXO3a were observed using western blot.

Results

At the end of the experiment, the levels of SCr, BUN and malondialdehyde (MDA) were all increased in the CM group. The LAG and HAG reduce superoxide anion (SOD) activity, catalase (CAT) activity, glutathione peroxidase (GPx) activity and glutathione (GSH) content, as well as SCr and BUN level. Moreover, apoptosis-associated proteins, caspase 3 p17, bax and bcl-2 were upregulated. In HK-2 cells, after adding iohexol, proliferation and intracellular ROS levels were significantly increased. Using astaxanthin in advance after the intervention, the result is opposite. SIRTl inhibitors NA can reduce the expression of SIRTl and decrease the expression of FOXO3a protein. Si-RNA FOXO3a reduces the expression of FOXO3a but had no significant effect on the expression of SIRT1.

Conclusions

Our study demonstrates that the intervention of astaxanthin could attenuate the oxidative stress and apoptosis in contrast-induced acute kidney injury (CI-AKI), and the SIRT1/FOXO3a pathway participates in the contrast-induced apoptosis of HK-2 cells. Finally, astaxanthin reduces CI-AKI by suppression of apoptosis, which may be through inhibition of SIRT1/FOXO3a pathways.

Keywords

Astaxanthin Contrast-induced acute kidney injury Oxidative stress Cell apoptosis 

Notes

Acknowledgements

This study was financially supported by a grant from the Six talent peaks project in Jiangsu Province (2014-YY-007) given to Wenhua Li.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interest.

Supplementary material

11255_2018_1788_MOESM1_ESM.docx (658 kb)
Supplementary material 1 (DOCX 657 kb)

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Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • Nana Liu
    • 1
  • Jing Chen
    • 2
  • Dongmei Gao
    • 1
  • Wenhua Li
    • 1
    • 3
    Email author
  • Di Zheng
    • 3
  1. 1.Institute of Cardiovascular Disease ResearchXuzhou Medical UniversityXuzhouChina
  2. 2.Department of EchocardiographyThe First People’s Hospital of HuaianHuaianChina
  3. 3.Department of CardiologyThe Affiliated Hospital of Xuzhou Medical UniversityXuzhouChina

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