Hepatocellular Metabolic Abnormalities Induced by Long-Term Exposure to Novel Brominated Flame Retardant, Hexabromobenzene

Novel brominated flame retardants (NBFRs) are widely used to avoid environmental accumulation concerns and because of the regulations imposed on classical BFRs. However, recent studies have not revealed the negative effects of NBFR accumulation and exposure on humans. We conducted a metabolomics study on hexabromobenzene (HBB), one of the NBFRs, to investigate its effect on hepatocytes. Gas chromatography-mass spectrometry-based metabolite profiling was performed to observe metabolic perturbations by treating human livertissue-derived HepG2 cell lines with HBB for maximum 21 days. Metabolic pathway enrichment using 17 metabolite biomarkers determined via univariate and multivariate statistical analysis verified that long-term accumulation of HBB resulted in distinct diminution of eight amino acids and five other metabolites. Molecular docking of the biomarker-related enzymes revealed the potential molecular mechanism of hepatocellular response to HBB exposure, which disrupts the energy metabolism of hepatic cells. Collectively, this study may provide insights into the hidden toxicity of bioaccumulating HBB and unveil the risks associated with non-regulated NBFRs.

Automated summary

Recent studies have found that long-term accumulation and exposure to novel brominated flame retardants (NBFRs) have negative effects on human health, leading to metabolic abnormalities and disruption of energy metabolism in liver cells. Metabolomics study revealed that accumulation of HBB (one of the NBFRs) resulted in significant reduction of amino acids and other metabolites. Molecular docking analysis suggested that HBB exposure may disrupt the energy metabolism of hepatic cells. This study provides insights into the hidden toxicity of non-regulated NBFRs.