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

Abstract

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.

Keywords: Apoptosis; Cadmium; Mitochondrion; Oxidative stress; Renal tubular epithelial cell.