Tetrabromobisphenol A and Cadmium Chloride Induced Hepatic Oxidative Stress and Autophagy Inhibition in Rats

Tetrabromobisphenol A (TBBPA) and Cadmium (Cd) are environmentally ubiquitous and coexisting contaminants, yet the consequences of joint exposure remain to be further clarified. This study employed rats to elucidate effects on oxidative stress and autophagy in the liver exposed to these compounds at environment-relevant doses. Results showed that TBBPA or/and CdCl₂ altered hepatic injury biomarkers, along with obvious histopathological alterations. Besides, oxidative stress indicators were elevated, whereas mRNA expressions and activities of antioxidant enzymes were decreased, and Nrf2 signaling pathway exhibited a failure of homeostatic activation, with reduced expression of key factors, following TBBPA and CdCl₂ exposure. Further, autophagy inhibition was triggered, which appeared as up-regulating mRNA and protein expressions of key factors. More importantly, changes above were more evident in the combined groups than individual groups. Taken together, these results suggested that environmental doses of TBBPA and CdCl₂ may exacerbate hepatic abnormalities in terms of inducing oxidative stress via Nrf2 signaling pathway and autophagy inhibition.