Assessment of 9-oh-and 7,8-diol-benzo[a]pyrene in blood as potent markers of cognitive impairment related to benzo[a]pyrene exposure: An animal model study

Lynda Saber Cherif, Lei Cao-Lei, Sophie Farinelle, Claude P. Muller, Jonathan D. Turner, Henri Schroeder, Nathalie Grova*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

Abstract

The potent neurotoxicity of benzo[a]pyrene (B[a]P) has been suggested to be a suscepti-bility factor accelerating the onset of brain tumours and the emergence of neurobehavioural dis-turbances. B[a]P has been shown to be neurotoxic, acting directly on both the central and peripheral nervous systems, as well as indirectly via peripheral organs like liver and gut. By using a realistic B[a]P exposure scenario (0.02–200 mg/kg/day, 10 days) in mice, we elucidated brain-specific B[a]P metabolism and at identified hydroxylated B[a]P metabolites in serum which could be used as markers of cognitive impairment. Repeated oral administration of B[a]P led to, at the doses of 20 and 200 mg/kg/day, significant overexpression of Cyp1a1/Cyp1b1 in 2 out of the 3 brain regions considered, thereby suggesting the ability of the brain to metabolize B[a]P itself. At the same doses, mice exhibited a reduction in anxiety in both the elevated plus maze and the hole board apparatus. Concomitantly, B[a]P triggered dose-dependent changes in Nmda subunit expression (Nr1 and Nr2a/Nr2b) in areas involved in cognition. We detected 9-OH-B[a]P and 7,8-diol-B[a]P in serum at the level for which cognitive impairment was observed. We suggest that these metabolites may, in the future be exploited as potent biomarkers of B[a]P-induced cognitive impairments.

Original languageEnglish
Article number50
JournalToxics
Volume9
Issue number3
DOIs
Publication statusPublished - 8 Mar 2021

Keywords

  • 9-OHbenzo[a]pyrene 7,8-diol-benzo[a]pyrene
  • Benzo[a]pyrene
  • Biomarker of neurotoxicity
  • Cognitive impairments
  • Metabolism
  • NMDA receptor
  • Oral exposure

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