Open Access

Resveratrol alleviates the cytotoxicity induced by the radiocontrast agent, ioxitalamate, by reducing the production of reactive oxygen species in HK-2 human renal proximal tubule epithelial cells in vitro

  • Authors:
    • Yen Ta Huang
    • Yi Ya Chen
    • Yu Hsien Lai
    • Chuan Chu Cheng
    • Tzu Chun Lin
    • Ying Shih Su
    • Chin Hung Liu
    • Pei Chun Lai
  • View Affiliations

  • Published online on: November 9, 2015     https://doi.org/10.3892/ijmm.2015.2404
  • Pages: 83-91
  • Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Radiocontrast-induced nephropathy (RIN) is one of the leading causes of hospital-acquired acute kidney injury (AKI). The clinical strategies currently available for the prevention of RIN are insufficient. In this study, we aimed to determine whether resveratrol, a polyphenol phytoalexin, can be used to prevent RIN. For this purpose, in vitro experiments were performed using a human renal proximal tubule epithelial cell line (HK-2 cells). Following treatment for 48 h, the highly toxic radiocontrast agent, ioxitalamate, exerted cytotoxic effects on the HK-2 cells in a concentration-dependent manner, as shown by MTT assay. The half maximal inhibitory concentration (IC50) was found to be approximately 30 mg/ml. Flow cytometry also revealed a marked increase in the number of apoptotic cells following exposure to ioxitalamate. In addition, the number of necrotic, but not necroptotic cells was increased. However, treatment with resveratrol (12.5 µM) for 48 h significantly alleviated ioxitalamate (30 mg/ml)-induced cytotoxicity, by reducing cytosolic DNA fragmentation, increasing the expression of the anti-apoptotic protein, Bcl-2 (B-cell lymphoma 2), and survivin, activating caspase-3, preventing autophagic death and suppressing the production of reactive oxygen species (ROS). Resveratrol also suppressed the ioxitalamate-induced formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage. N-acetylcysteine (NAC), a ROS scavenger commonly used to prevent RIN, also reduced ioxitalamate-induced cytotoxicity, but at a high concentration of 1 mM. Sirtuin (SIRT)1 and SIRT3 were not found to play a role in these effects. Overall, our findings suggest that resveratrol may prove to be an effective adjuvant therapy for the prevention of RIN.
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January-2016
Volume 37 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Huang YT, Chen YY, Lai YH, Cheng CC, Lin TC, Su YS, Liu CH and Lai PC: Resveratrol alleviates the cytotoxicity induced by the radiocontrast agent, ioxitalamate, by reducing the production of reactive oxygen species in HK-2 human renal proximal tubule epithelial cells in vitro. Int J Mol Med 37: 83-91, 2016.
APA
Huang, Y.T., Chen, Y.Y., Lai, Y.H., Cheng, C.C., Lin, T.C., Su, Y.S. ... Lai, P.C. (2016). Resveratrol alleviates the cytotoxicity induced by the radiocontrast agent, ioxitalamate, by reducing the production of reactive oxygen species in HK-2 human renal proximal tubule epithelial cells in vitro. International Journal of Molecular Medicine, 37, 83-91. https://doi.org/10.3892/ijmm.2015.2404
MLA
Huang, Y. T., Chen, Y. Y., Lai, Y. H., Cheng, C. C., Lin, T. C., Su, Y. S., Liu, C. H., Lai, P. C."Resveratrol alleviates the cytotoxicity induced by the radiocontrast agent, ioxitalamate, by reducing the production of reactive oxygen species in HK-2 human renal proximal tubule epithelial cells in vitro". International Journal of Molecular Medicine 37.1 (2016): 83-91.
Chicago
Huang, Y. T., Chen, Y. Y., Lai, Y. H., Cheng, C. C., Lin, T. C., Su, Y. S., Liu, C. H., Lai, P. C."Resveratrol alleviates the cytotoxicity induced by the radiocontrast agent, ioxitalamate, by reducing the production of reactive oxygen species in HK-2 human renal proximal tubule epithelial cells in vitro". International Journal of Molecular Medicine 37, no. 1 (2016): 83-91. https://doi.org/10.3892/ijmm.2015.2404