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Biomed Pharmacother. 2019 Jan;109:2309-2317. doi: 10.1016/j.biopha.2018.11.108. Epub 2018 Nov 29.

Icariin ameliorates cisplatin-induced cytotoxicity in human embryonic kidney 293 cells by suppressing ROS-mediated PI3K/Akt pathway.

Author information

1
College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118 China.
2
College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118 China; Intelligent Synthetic Biology Center, Daejeon 34141 Republic of Korea.
3
School of Biomedical Sciences, University of Queensland, Brisbane 4072, Australia.
4
Department of Nephrology, China-Japan Union Hospital of Jilin University, Changchun 130033 China.
5
College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118 China. Electronic address: rs0109@163.com.
6
College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118 China. Electronic address: liwei7727@126.com.

Abstract

Cisplatin, as an effective chemotherapeutic agent, is widely used to treat verious types of cancers. Nephrotoxicity induced by cisplatin seriously limits its clinical application. Icariin, a major and remarkable flavonoid isolated from Epimedium koreanum, has been reported to exert anti-oxidative stress and anti-inflammation actions. The purpose of this study is to explore the protective effect and possible mechanism of icariin on cisplatin-induced nephrotoxicity on HEK-293 cells. In this study, icariin pretreatment for 24 h significantly ameliorated cisplatin-induced oxidative stress by reducing levels of malondialdehyde (MDA) and reactive oxygen species (ROS), while increasing level of glutathione (GSH) in HEK-293 cells. Furthermore, icariin pretreatment reduced NF-κB phosphorylation and nuclear translocation in HEK-293 cells followed by decreased secretion of IL-1β, TNF-α, and iNOS, suggesting a suppression of inflammatory response. Moreover, icariin pretreatment significantly reduced cellular apoptosis via reduced levels of Bax, cleaved caspase-3/9, and increased anti-apoptotic protein Bcl-2 in the cells. Importantly, LY294002, a specific PI3K inhibitor, abrogated the anti-apoptosis effect of icariin, implicating the involvement of PI3K/Akt pathway. In summary, icariin prevents cisplatin-induced HEK-293 cell injury by inhibiting oxidative stress, inflammatory response, and cellular apoptosis partly via regulating NF-κB and PI3K/Akt signaling pathways. Icariin may serve as a potential therapeutic target against cisplatin-induced nephrotoxicity.

KEYWORDS:

Cisplatin; Cytotoxicity; HEK-293 cells; Icariin; PI3K/Akt

PMID:
30551489
DOI:
10.1016/j.biopha.2018.11.108
[Indexed for MEDLINE]
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