TBBPA induced ROS overproduction promotes apoptosis and inflammation by inhibiting autophagy in mice lung

Abstract

Tetrabromobisphenol A (TBBPA), a non-degradable environmental pollutant, was discharge into the air during the manufacture, use and recycling of plastic products. Respiratory exposure is the main way to inhalation of TBBPA. However, the research on the damage of TBBPA to the respiratory system is still extremely few. The aim of this experiment was to explore the mechanism of TBBPA toxicity to the lungs. Forty C57BL/6 J mice randomly divided into 4 groups, and the experimental groups with TBBPA at 10 n M/kg, 20 n M/kg and 40 n M/kg for 14 consecutive days. Histopathological and ultrastructural analysis showed that the inflammatory cells infiltrated and tissue structure damaged in the lung of mice with exposing to TBBPA. The ROS and MDA levels increase and the T-AOC, GSH-Px, CAT, SOD activities inhibition was found in lung tissue with TBBPA exposure. The expression of autophagy-related factors Beclin-1, P62, LC3-II, ATG5, and ATG7 decreased. The activation of NF-κB/TNF-α pathway indicates the occurrence of inflammation. The expression of Bax, caspase3, caspase7, caspase 9 increase, the expression of Bcl-2 decreased, and the apoptosis pathway activated. The autophagy inducer rapamycin can reverse the adverse effects of inflammation and apoptosis. Taken together, TBBPA inhibits autophagy-induced pneumonia and apoptosis by overproduction ROS.

Keywords

• Tetrabromobisphenol A
• Oxidative stress
• Autophagy
• Inflammation
• Apoptosis