Individuals are exposed to toxic chemicals on a daily basis. Some toxic chemicals produce reactive oxygen species (ROS), which contribute to protein modification and the accumulation of protein carbonyl groups. The antioxidant response to ROS involves the binding of nuclear factor-erythroid 2 subunit-related transcription factors (NFE2L or Nrfs) to antioxidant response elements (AREs)/electrophile response elements (EpREs), located in the promoter and enhancer regions of antioxidant and detoxification enzymes. Activation of the AREs/EpREs pathway, in particular by Nrf proteins, in response to penta-brominated diphenyl ether (penta-BDE, BDE-99) flame retardant, was observed. Protein damage (as assessed protein carbonyl assays), lipid damage (as assessed by oxidation assays), and the activation of the beta-galactosidase enzyme occurred as a results of penta-BDE treatment. These results provide insight into how penta-BDE a) initiates the antioxidant response, b) damages proteins and lipids through ROS and c) increases beta-galactosidase activity.