Panax notoginseng saponins mitigate cisplatin induced nephrotoxicity by inducing mitophagy via HIF-1α
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Xueyan Liang2, Yufang Yang1, Zhenguang Huang1, Jinling Zhou2, Yue’e Li2 and Xiaobin Zhong3
1Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
2Postgraduate, Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
3Regenerative Medicine Research Center of Guangxi Medical University, Nanning, China
Yufang Yang, email: [email protected]
Xiaobin Zhong, email: [email protected]
Keywords: panax notoginseng saponins; cisplatin-induced nephrotoxicity; mitophagy; HIF-1α
Received: November 15, 2016 Accepted: July 12, 2017 Published: August 03, 2017
We investigated the role of HIF-1α in the mitigation of cisplatin-induced nephrotoxicity by Panax notoginseng saponins (PNS) in a rat model. Serum creatinine (Scr), blood urea nitrogen (BUN) and urinary N-acetyl-β-D-glucosaminidase (NAG) levels were all elevated in cisplatin treated rats. PNS reduced Scr, BUN and NAG levels in the presence or absence of the HIF-1α inhibitor 2-methoxyestradiol (2ME2). PNS also reduced the high tubular injury scores, which corresponded to renal tubular damage in cisplatin-treated rats and which were exacerbated by 2ME2. Renal tissues from PNS-treated rats showed increased HIF-1α mRNA and nuclear localized HIF-1α protein. Moreover, PNS treatment increased BNIP3 mRNA as well as LC3-II, BNIP3 and Beclin-1 proteins and the LC3-II/LC3-I ratio in rat renal tissues. This suggested that PNS treatment enhanced HIF-1α, which in turn increased autophagy. This was confirmed in transmission electron micrographs of renal tissues that showed autophagosomes in PNS-treated renal tissues. These findings demonstrate that PNS mitigates cisplatin-induced nephrotoxicity by enhancing mitophagy via a HIF-1α/BNIP3/Beclin-1 signaling pathway.
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