Sub-lethal Doses of Polybrominated Diphenyl Ethers, in Vitro, Promote Oxidative Stress and Modulate Molecular Markers Related to Cell Cycle, Antioxidant Balance and Cellular Energy Management

Abstract

In the present study, we evaluated the effects of different concentrations of the polybrominated diphenyl ethers (PBDEs) BDE-209, BDE-47 and BDE-99, on the vitality and oxidative stress of a HS-68 human cell culture exposed to the compounds for three days. The results showed that for this exposure time, only the highest concentrations produced a significant vitality reduction and oxidative stress induction (p < 0.05), measured as reactive oxygen species (ROS). Subsequently, in order to verify the effects of sub-lethal doses, cells were exposed for a longer time and data collected, after 12 and 20 days, to study ROS production and some molecular markers related to cell cycle and stress (p53, pRB, PARP, c-Jun and c-Fos), antioxidant status and proliferation (ERK, c-Jun and c-Fos), energy balance (NRF2, AMPK, HIF). Most of the biomarkers were influenced by the treatments, indicating that sub-lethal doses of PBDEs, for longer time, can enhance the production of ROS, altering the energetic metabolism, cell cycle and antioxidant balance, determining possible negative effects on the cell proliferation equilibrium.