Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Z-ligustilide reduces cisplatin-induced nephrotoxicity via activation of NRF2/HO-1 signaling pathways

Xu Chen^1,2, Yingjie Cao², Naifeng Guo², Guoyuan Lu¹

¹Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006; ²Department of Nephrology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, China.

For correspondence:- Guoyuan Lu Email: luguoyuan947@163.com Tel:+8613776061947

Accepted: 28 June 2020 Published: 31 July 2020

Citation: Chen X, Cao Y, Guo N, Lu G. Z-ligustilide reduces cisplatin-induced nephrotoxicity via activation of NRF2/HO-1 signaling pathways. Trop J Pharm Res 2020; 19(7):1359-1364 doi: 10.4314/tjpr.v19i7.3

© 2020 The authors.
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Abstract

Purpose: To investigate the effect of Z-ligustilide (Z-lig) on cisplatin-induced nephrotoxicity and examine whether NRF2 signaling mediates the underlying mechanism of action.

Methods: Human proximal tubular epithelial cells (HK-2) were pretreated with 20 or 100 µM Z-lig for 2 h, followed by 10 μM cisplatin treatment for 24 h. Cell viability was measured using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A commercial kit was used to determine lactate dehydrogenase (LDH) release. Apoptosis was determined by flow cytometry while Western blotting was used to evaluate protein levels. Levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) were assessed by enzyme-linked immunosorbent assay (ELISA).

Results: Cisplatin decreased HK-2 cell viability and increased LDH release, while Z-lig increased cell viability and decreased LDH release in a dose-dependent manner (p < 0.05). Moreover, Z-lig reduced cisplatin-induced apoptosis (p < 0.01), and alleviated cellular oxidative stress caused by cisplatin (p < 0.05). Furthermore, Z-lig activated NRF2/HO-1 signaling in cells treated with cisplatin (p < 0.05).

Conclusion: Z-lig reduces cisplatin-induced nephrotoxicity via activation of NRF2/HO-1 signaling. Thus, Z-lig is a potential drug for the treatment of nephrotoxicity caused by cisplatin

Keywords: Z-ligustilide, Cisplatin, Nephrotoxicity, Oxidative stress, Apoptosis, Nuclear factor erythroid 2-related factor 2, Heme oxygenase-1