Propolis Suppresses CdCl2-Induced Cytotoxicity of COS7 Cells through the Prevention of Intracellular Reactive Oxygen Species Accumulation

Propolis is a natural product made by honeybees and contains various compounds, including flavonoids, amino acids and fatty acids. These compounds are considered to have antiviral, antibacterial and antioxidative properties. On the other hand, cadmium (Cd), an industrial and environmental pollutant, preferentially accumulates in the kidney and induces kidney injury. We previously reported that exposure to CdCl2 induced cell death though intracellular reactive oxygen species (ROS) generation in kidney tubule epithelial COS7 cells. Here, we investigated whether propolis extracts suppress CdCl2-induced cytotoxicity. Predictably, pretreatment with propolis extracts significantly suppressed CdCl2-induced cytotoxicity and intracellular ROS generation. Propolis extracts not only showed superoxide dismutase and antioxidative activities, but also increased the expression of heme oxygenase-1 (HO-1), an antioxidative enzyme. Moreover, we determined the involvement of hypoxia inducible factor-1 alpha in propolis extract-derived HO-1 induction. We demonstrate for the first time the utility of propolis for Cd-related COS7 cytotoxicity, and these novel findings are considered to contribute to the control of ROS-derived disorders.