Multi-organ biochemical perturbations induced by chronic benzo[b]fluoranthene exposure involve oxidative stress and inflammatory response in Balb/c mice.

BACKGROUND: Benzo[b]fluoranthene (BbF) is a bioaccumulative high-molecular-weight polycyclic aromatic hydrocarbon (PAH) with documented multi-organ toxicity, yet the systemic effects of chronic oral exposure remain poorly characterized. This study tested the hypothesis that prolonged BbF exposure induces dose-dependent oxidative and inflammatory perturbations, leading to tissue-specific biochemical injury across major visceral organs. RESULTS: Male Balb/c mice were orally exposed to 2, 8, and 16 mg kg-1 d-1 BbF for 12 weeks. BbF exposure induced dose-dependent oxidative stress, characterized by elevated reactive oxygen species and malondialdehyde levels and decreased activities of superoxide dismutase, catalase, and glutathione peroxidase, accompanied by transcriptional downregulation of Nrf2/HO-1 antioxidant-related genes. Concurrently, tissue HMGB1 protein accumulated in a dose- and organ-dependent manner, with hepatic HMGB1 increased by 58.32% at the highest dose, correlating with higher transcript levels of the NF-κB p65/NLRP3 cascade and increased pro-inflammatory cytokine (IL-1β, TNF-α, IL-6) abundance. Energy metabolism was also disrupted, with high-dose BbF reducing ATP levels by 59.52% (liver) and 55.52% (heart), and suppressing lactate dehydrogenase activity by 31.40% and 30.81%, respectively. Organ-specific biomarkers (hepatic alanine aminotransferase/aspartate aminotransferase, renal Kim-1, cardiac cTn-I, splenic IgG) confirmed multi-organ biochemical perturbations. The liver and heart showed the most pronounced changes, reflecting their intrinsic vulnerability conferred by high metabolic activity and mitochondrial abundance. CONCLUSION: Chronic BbF exposure elicits dose-dependent multi-organ biochemical perturbations, correlating with transcriptional changes in the Nrf2/HO-1 and NF-κB/NLRP3 pathways and concurrent energy metabolism disturbance. These correlative findings provide in vivo evidence that supports hazard characterization of BbF and yields foundational data for future risk-assessment strategies for high-molecular-weight PAHs. © 2026 Society of Chemical Industry.