Research Papers:

GSPE reduces lead-induced oxidative stress by activating the Nrf2 pathway and suppressing miR153 and GSK-3β in rat kidney

Biying Liu, Haili Zhang, Xiao Tan, Daqian Yang, Zhanjun Lv, Huijie Jiang, Jingjing Lu, Ruiqi Baiyun and Zhigang Zhang _

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Oncotarget. 2017; 8:42226-42237. https://doi.org/10.18632/oncotarget.15033

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Biying Liu1, Haili Zhang1, Xiao Tan1, Daqian Yang1, Zhanjun Lv1, Huijie Jiang1, Jingjing Lu1, Ruiqi Baiyun1 and Zhigang Zhang1

1College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China

Correspondence to:

Zhigang Zhang, email: [email protected]

Keywords: grape seed procyanidin extract, kidney injury, oxidative stress, Nrf2, nephroprotective effect

Received: September 24, 2016    Accepted: January 16, 2017    Published: February 02, 2017


Lead (Pb) is a global environmental health hazard that leads to nephrotoxicity. However, the effective treatment of Pb-induced nephrotoxicity remains elusive. Grape seed procyanidin extract (GSPE) has beneficial properties for multiple biological functions. Therefore, the present study investigated whether GSPE reduced Pb-induced nephrotoxicity as well as the protective mechanism of GSPE in a well-established 35-day Pb induced nephrotoxicity rat model. The results showed that GSPE normalized Pb-induced oxidative stress, histological damage, inflammatory, apoptosis, and changes of miR153 and glycogen synthase kinase 3β (GSK-3β) levels in rat kidney. Moreover, GSPE enhanced the induction of phase II detoxifying enzymes (heme oxygenase-1 and NAD(P)H quinone oxidoreductase 1) by increasing nuclear factor-erythroid-2-related factor 2 (Nrf2) expression. This study identifies for the first time that Pb-induced oxidative stress in rat kidney is attenuated by GSPE treatment via activating Nrf2 signaling pathway and suppressing miR153 and GSK-3β. Nrf2 signaling provides a new therapeutic target for renal injury induced by Pb, and GSPE could be a potential natural agent to protect against Pb-induced nephrotoxicity.

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