Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Evodiamine attenuates cadmium-induced nephrotoxicity through activation of Nrf2/HO-1 pathway

Zhichun Song¹, Wei Wang¹, Xiaoren Zhang², Hongsheng Yu³, Chunsheng Qu¹, Shu Dai¹, Xiaodong Wang⁴

¹Department of Clinical Laboratory, Lishui People’s Hospital, Lishui City; ²Department of Clinical Laboratory, Ningbo Medical Center Lihuili Eastern Hospital, Ningbo City, Zhejiang Province 315040; ³Department of Clinical Laboratory, Wuhan Children's Hospital, Wuhan City, Hubei Province 430016; ⁴Department of Rheumatology and Immunology, Lishui People's Hospital, Lishui City, Zhejiang Province 323000, China.

For correspondence:- Xiaodong Wang Email: wangxiaodong1224@126.com Tel:+865782780125

Accepted: 25 July 2021 Published: 31 August 2021

Citation: Song Z, Wang W, Zhang X, Yu H, Qu C, Dai S, et al. Evodiamine attenuates cadmium-induced nephrotoxicity through activation of Nrf2/HO-1 pathway. Trop J Pharm Res 2021; 20(8):1579-1584 doi: 10.4314/tjpr.v20i8.5

© 2021 The authors.
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Abstract

Purpose: To investigate the protective role of evodiamine, a naturally occurring anti-inflammatory, antioxidant, and anti-apoptotic compound, against cadmium-induced cytotoxicity in proximal tubular cells (human kidney 2; HK-2).

Methods: HK-2 cells were treated with different concentrations of evodiamine (5, 20, 50 μM) for 2 h and then incubated with 40 µM cadmium chloride for another 24 h. Cell viability and apoptosis were evaluated using thiazolyl blue tetrazolium bromide (MTT) and flow cytometry, respectively. Oxidative stress was assayed by measuring the levels of malonaldehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-PX).

Results: Cadmium chloride treatment in HK-2 cells significantly reduced cell viability (p < 0.01) and increased apoptosis compared to the control. Evodiamine pretreatment attenuated the cadmium chloride-provoked decrease in cell viability and increase in apoptosis. Evodiamine also decreased expression of cleaved caspase-3 and cleaved caspase-9 in HK-2 cells. Cadmium chloride exposure provoked kidney injury, as evidenced by increased MDA levels and decreased SOD, GSH, and GSH-PX levels. Pretreatment with evodiamine ameliorated kidney injury, as shown by decreased MDA expression and increased SOD, GSH, and GSH-PX expression. Evodiamine exposure significantly enhanced protein expression of nuclear factor erythropoietin-2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1).

Conclusion: Evodiamine exerts an anti-apoptotic and anti-oxidative effect against cadmium chloride-induced nephrotoxicity via Nrf2/HO-1 pathway activation. These findings represent a potential therapeutic strategy for cadmium-provoked nephrotoxicity.

Keywords: Evodiamine, Cadmium, Nephrotoxicity, Nrf2/HO-1, Apoptosis, Oxidative stress