Open AccessEvodiamine attenuates cadmium-induced nephrotoxicity through activation of Nrf2/HO-1 pathway
Author(s) -
Zhimin Song,
Wei Wang,
Xiaoren Zhang,
Hongsheng Yu,
Chunsheng Qu,
Shixun Dai,
Xiaodong Wang
Publication year - 2022
Publication title -
tropical journal of pharmaceutical research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.209
H-Index - 36
eISSN - 1596-5996
pISSN - 1596-9827
DOI - 10.4314/tjpr.v20i8.5
Subject(s) - evodiamine , chemistry , cadmium chloride , glutathione , superoxide dismutase , nephrotoxicity , viability assay , oxidative stress , apoptosis , glutathione peroxidase , pharmacology , cadmium , biochemistry , toxicity , enzyme , biology , organic chemistry , chromatography
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.