Fluorinated liquid crystal monomer (FLCM) induces kidney dysfunction by disrupting PPARα-mediated fatty acid oxidation: In vivo, in vitro, and in silico assays

Abstract

Fluorinated liquid crystal monomers (FLCMs) are ubiquitous in our daily life as being the units of liquid crystal displays, yet their toxicological impacts remain largely unexplored. Herein, this study presents a comprehensive investigation into the hazardous effects of 3,4-difluoro-4′-(trans-4-ethylcyclohexyl)-biphenyl (DFECB), a representative biphenyl FLCM, using in vivo, in vitro, and in silico approaches. Mice exposed to human-relevant concentrations of DFECB for 30 days exhibited renal dysfunction, characterized by interstitial inflammation, glomerular morphological changes and metabolic disorders. Metabolomic profiling revealed inhibited fatty acid β-oxidation as a key factor in renal impairment, correlating with significant downregulation of peroxisome proliferator-activated receptor α (PPARα). In vitro assays demonstrated DFECB-induced cytotoxicity, oxidative stress, inflammation and energy deficit in renal cells. Importantly, pretreatment with the PPARα agonist mitigated the adverse effects of DFECB, underscoring the central role of PPARα in DFECB-induced nephrotoxicity. Molecular docking simulations elucidated strong halogen and hydrophobic interactions between DFECB and PPARα, providing mechanistic insights. Collectively, these results suggested that DFECB could act as a disruptor of the PPARα-mediated fatty acid metabolism pathway, leading to renal dysfunction. This study highlights the potential health risks associated with FLCMs and emphasizes the need for their scientific regulation and further toxicological investigation.