Work

Biotransformation of three hexabromocyclododecane diastereoisomers in HepG2 cells and their cellular metabolomics

Year: 2026

Type: article

Abstract: In this study, human hepatoma cells (HepG2) were exposed to three concentrations (0.05, 1 and 10 mg/L) of individual hexabromocyclododecane (HBCD) diastereoisomers (α-, β- and γ-HBCD) for 24 h to investigate their cytotoxicity, biotransformation, bioisomerization, and induced metabolic disturbances. All isomers showed cytotoxicity, as indicated by dose-dependent decreases cell viability (γ-HBCD > β-HBCD > α-HBCD) and significant GSH depletion (β-HBCD > α-HBCD > γ-HBCD). While their cellular apparent uptake rates were similar, β-HBCD had a higher biotransformation rate than α- and γ-HBCD. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) identified putative pentabromocyclododecene (PBCDe) as the main metabolite, with varying levels among isomers. Bioisomerization (β/γ-HBCD to α-HBCD; β-HBCD to γ-HBCD) and reductive debromination were the major metabolic pathways. Metabolomic analysis revealed HBCD disrupted multiple metabolic pathways (e.g., choline, glycerophospholipid, fatty acid, purine metabolism), with distinct effects observed across different diastereoisomers.

Source: Ecotoxicology and Environmental Safety

DOI: 10.1016/j.ecoenv.2026.120383