Cadmium induces oxidative stress and apoptosis in lung epithelial cells

• Published in: Toxicology mechanisms and methods 2016-11, Vol.26 (9), p.658-666
• Main Authors: Kiran Kumar, K. M., Naveen Kumar, M., Patil, Rajeshwari H., Nagesh, Rashmi, Hegde, Shubha M., Kavya, K., Babu, R. L., Ramesh, Govindarajan T., Sharma, S. Chidananda
• Format: Article
• Language: English
• Subjects: A549 Cells; Antioxidants - metabolism; Apoptosis; Apoptosis - drug effects; Cadmium; Cadmium - toxicity; Cell Culture Techniques; Cell Survival - drug effects; Dose-Response Relationship, Drug; Environmental Pollutants - toxicity; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelial Cells - pathology; FACS; Flow Cytometry; Humans; Lipid Peroxidation - drug effects; Lung - drug effects; Lung - metabolism; Lung - pathology; Oxidative Stress - drug effects; Reactive Oxygen Species - metabolism; ROS; RT-PCR; SOD
• ISSN: 1537-6516; 1537-6524
• DOI: 10.1080/15376516.2016.1223240

Cadmium (Cd) is one of the well-known highly toxic environmental and industrial pollutants. Cd first accumulates in the nucleus and later interacts with zinc finger proteins of antiapoptotic genes and inhibit the binding of transcriptional factors and transcription. However, the role of Cd in oxidative stress and apoptosis is less understood. Hence, the present study was undertaken to unveil the mechanism of action. A549 cells were treated with or without Cd and cell viability was measured by MTT assay. Treatment of cells with Cd shows reduced viability in a dose-dependent manner with IC 50 of 45 μM concentration. Cd significantly induces the reactive oxygen species (ROS), lipid peroxidation followed by membrane damage with the leakage of lactate dehydrogenase (LDH). Cells with continuous exposure of Cd deplete the antioxidant super oxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzymes. Further, analysis of the expression of genes involved in apoptosis show that both the extrinsic and intrinsic apoptotic pathways were involved. Death receptor marker tumor necrosis factor-α (TNF-α), executor caspase-8 and pro-apoptotic gene (Bax) were induced, while antiapoptotic gene (Bcl-2) was decreased in Cd-treated cells. Fluorescence-activated cell sorting (FACS) analysis further confirms the induction of apoptosis in Cd-treated A549 cells.