Issue 46, 2013

Functionalized selenium nanoparticles with nephroprotective activity, the important roles of ROS-mediated signaling pathways

Abstract

The most frequent adverse effect of cisplatin-based chemotherapy is nephrotoxicity. Oxidative stress has been implicated as an important mechanism in the pathogenesis of cisplatin-induced nephrotoxicity. In the present study, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (trolox) surface-functionalized selenium nanoparticles (Se@Trolox) with enhanced antioxidant activity have been prepared by self-assembly of trolox on the surface of the nanoparticles, and their nephroprotective effects have been investigated. Functionalization by trolox significantly enhanced cell uptake and in vitro antioxidant activities of the nanoparticles. In addition, pretreatment with Se@Trolox dose-dependently blocked cisplatin-induced cell growth inhibition against HK-2 cells. Mechanistic investigation suggested that Se@Trolox markedly prevented cisplatin-induced apoptosis in HK-2 cells, as evidenced by inhibition of chromatin condensation, DNA fragmentation, PARP cleavage and activation of caspase-3. Furthermore, Se@Trolox effectively blocked the cisplatin-induced reactive oxygen species (ROS) accumulation, activation of AKT and MAPK signaling and DNA damage-mediated p53 phosphorylation in HK-2 cells. Taken together, our findings suggest that Se@Trolox is a promising Se species with potential application in prevention of cisplatin-induced renal injury.

Graphical abstract: Functionalized selenium nanoparticles with nephroprotective activity, the important roles of ROS-mediated signaling pathways

Article information

Article type
Paper
Submitted
20 Aug 2013
Accepted
30 Sep 2013
First published
01 Oct 2013

J. Mater. Chem. B, 2013,1, 6365-6372

Functionalized selenium nanoparticles with nephroprotective activity, the important roles of ROS-mediated signaling pathways

Y. Li, X. Li, W. Zheng, C. Fan, Y. Zhang and T. Chen, J. Mater. Chem. B, 2013, 1, 6365 DOI: 10.1039/C3TB21168A

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