BbF-induced liver injury in Balb/c mice: AhR activation as the conductor of metabolism, oxidative stress, lipid metabolism disorder, and inflammatory response.

Benzo[b]fluoranthene (BbF) is a known persistent organic environmental pollutant. This study aimed to analyze the influence of exposure to BbF on liver injury in Balb/c mice. After oral administration of BbF to male Balb/c mice for 12 weeks, the findings demonstrate that BbF exposure leads to reduced weight gain and hepatic oxidative stress, characterized by elevated ROS, MDA, and LPO levels. Additionally, it results in reduced activities of antioxidant enzymes. Furthermore, the presence of plasma lipid disorders along with increased hepatic free fatty acids and alterations in fatty acid composition indicate disturbances in lipid metabolism induced by BbF exposure. The observed elevation in proinflammatory cytokine levels suggests an inflammatory response induced by BbF. Additionally, the activation of AhR, and the increased levels of CYP enzyme revealed the metabolism activated of BbF toxic. The increased Keap1 and decreased Nrf2 and NQO1 mRNA and protein expression suggested the antioxidant system was damaged by BbF metabolism. AhR activation is associated with the inhibition of AMPK expression and subsequent upregulation of SREBP-1c and SCD1, which may contribute to the observed lipid metabolism disorders, and increased expression of NF-κB and Caspase-1 to make an inflammatory response. The findings of this study suggested that activation of the AhR pathway induced metabolic activation of BbF and then oxidative stress, meanwhile AhR activation suppressed the AMPK pathway, leading to dysregulation of lipid metabolism and inflammatory response. This study elucidated the underlying mechanism of BbF-induced hepatotoxicity and provided a foundation for comprehensive and systematic prevention strategies against environmental exposure to BbF.