Abstract
Cadmium (Cd) is a well-known heavy metal that causes environmental pollution and human health problems. Several studies attempted to assess Cd toxicity in vitro and in vivo. However, the systemic profile of cadmium toxicity has not been studied well. In the present study, we assessed the toxicity of Cd on human peripheral blood lymphocytes and monocytes and gene expression, using a system toxicological approach. Cd effect on cell viability and morphology were analyzed by MTT assay and AO/EB staining respectively. Mitochondrial membrane potential depletion and reactive oxygen singlet generation were assessed by flow cytometry. Effects of Cd treatment on gene expression were also studied. Significant reduction in cell viability and disintegration of nuclear morphology were observed in Cd-treated cells. Cd exposure enhanced the loss of mitochondrial membrane potential through oxidative stress. Dose-dependent upregulation of GSTM3 and downregulation of GSR gene expression were observed. TNF gene expression decreased as the level of Cd exposure increased. We analyzed the toxicological effects of Cd on more than 45 proteins for biological target identification. These system toxicological studies suggested that Cd induced toxicity through various biological processes such as oxidative stress, oxidation-reduction, and ROS and hydrogen peroxide generation. Additionally, Cd affects the cellular component network and modulates the expression level of oxidative stress-related genes.