Cadmium induces cytotoxicity through oxidative stress-mediated apoptosis pathway in duck renal tubular epithelial cells

• Published in: Toxicology in vitro 2019-12, Vol.61, p.104625, Article 104625
• Main Authors: Zhuang, Jionghan, Nie, Gaohui, Yang, Fan, Dai, Xueyan, Cao, Huabin, Xing, Chenghong, Hu, Guoliang, Zhang, Caiying
• Format: Article
• Language: English
• Subjects: Acetylcysteine; Acetylcysteine - pharmacology; Acidification; Animals; Antioxidants; Antioxidants - pharmacology; Apoptosis; Apoptosis - drug effects; Aquatic birds; Bcl-2 protein; Ca2+-transporting ATPase; Cadmium; Cadmium - toxicity; Calcium (intracellular); Calcium (mitochondrial); Calcium ions; Caspase-3; Catalase; Cells, Cultured; Cytotoxicity; Ducks; Epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Exposure; Gene expression; Glutathione; Glutathione peroxidase; Intracellular; Kidney Tubules - cytology; Kidneys; L-Lactate dehydrogenase; Lactate dehydrogenase; Lactic acid; Malondialdehyde; Membrane potential; Mitochondrion; Oxidative stress; Oxidative Stress - drug effects; Peroxidase; Reactive oxygen species; Renal tubular epithelial cell; Superoxide dismutase; Toxicity
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2019.104625

Cadmium (Cd) is a well studied nephrotoxic metal element. To investigate the effects of Cd-induced cytotoxicity on oxidative stress-mediated apoptosis in primary renal tubular epithelial cells of duck. Shaoxing duck (Anas platyrhyncha) renal tubular epithelial cells were cultured in medium in absence and presence of 3CdSO4·8H2O (1.25, 2.5, 5.0 μM Cd), in N-acetyl-l-cysteine (NAC) (100 μM), and the combination of Cd and NAC for 12 h. After 12 h exposure, morphologic observation and function, reactive oxygen species (ROS) level, antioxidant indices, the activity of ATPase, intracellular pH and [Ca2+]i, mitochondrial membrane potential (MMP), and apoptosis-related genes mRNA were determined. The results showed that Cd exposure could induce release of intracellular lactate dehydrogenase (LDH), simultaneously, enhance the ROS generation, acidification, malondialdehyde (MDA) and [Ca2+]i, decrease glutathione (GSH), Na+, K+-ATPase, Ca2+-ATPase, catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-Px) activities as well as MMP, upregulated Bak-1, Bax and Caspase-3 mRNA expression, inhibited Bcl-2 mRNA expression, and induced cell apoptosis. The toxicity of Cd to cells showed a dose-dependent manner. Antioxidant NAC could efficiently alleviate Cd-induced the cytotoxicity. Taken together, these results suggest that Cd exposure cause cytotoxicity through oxidative stress-mediated apoptosis pathway in duck renal tubular epithelial cells. •Cd induced oxidative stress by generating excessive ROS in duck renal tubular epithelial cells.•Apoptosis occurred in duck renal tubular epithelial cells treated with Cd.•Cd induced apoptosis through oxidative stress-mediated pathway in duck renal tubular epithelial cells.•N-acetyl-l-cysteine (NAC) has protective effects on Cd-induced cytotoxicity in duck renal tubular epithelial cells.