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Article

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

1
Calbinotox, EA7488, Faculty of Science and Technology, Lorraine University, 54500 Vandoeuvre-lès Nancy, France
2
Immune Endocrine Epigenetics Research Group, Department of Infection and Immunity, LuxembourgInstitute of Health, L-4354 Esch-sur-Alzette, Luxembourg
3
Experimental & Molecular Immunology Research Group, Department of Infection and Immunity, Luxembourg Institute of Health, L-4354 Esch-sur-Alzette, Luxembourg
4
Department of Infection and Immunity, Luxembourg Institute of Health, L-4354 Esch-Sur-Alzette, Luxembourg
5
Laboratoire National de Santé, L-3583 Dudelange, Luxembourg
*
Author to whom correspondence should be addressed.
Shared first authorship.
Current position, Research Institute of the McGill University Health Centre, Montreal, QC H3H 2R9, Canada.
§
Shared last authorship.
Academic Editors: João Teixeira and Radu-Corneliu Duca
Toxics 2021, 9(3), 50; https://doi.org/10.3390/toxics9030050
Received: 17 January 2021 / Revised: 14 February 2021 / Accepted: 3 March 2021 / Published: 8 March 2021
The potent neurotoxicity of benzo[a]pyrene (B[a]P) has been suggested to be a susceptibility factor accelerating the onset of brain tumours and the emergence of neurobehavioural disturbances. 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. View Full-Text
Keywords: benzo[a]pyrene; oral exposure; 9-OHbenzo[a]pyrene 7,8-diol-benzo[a]pyrene; biomarker of neurotoxicity; cognitive impairments; NMDA receptor; metabolism benzo[a]pyrene; oral exposure; 9-OHbenzo[a]pyrene 7,8-diol-benzo[a]pyrene; biomarker of neurotoxicity; cognitive impairments; NMDA receptor; metabolism
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MDPI and ACS Style

Cherif, L.S.; Cao-Lei, L.; Farinelle, S.; Muller, C.P.; Turner, J.D.; Schroeder, H.; Grova, N. 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. Toxics 2021, 9, 50. https://doi.org/10.3390/toxics9030050

AMA Style

Cherif LS, Cao-Lei L, Farinelle S, Muller CP, Turner JD, Schroeder H, Grova N. 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. Toxics. 2021; 9(3):50. https://doi.org/10.3390/toxics9030050

Chicago/Turabian Style

Cherif, Lynda S., Lei Cao-Lei, Sophie Farinelle, Claude P. Muller, Jonathan D. Turner, Henri Schroeder, and Nathalie Grova. 2021. "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" Toxics 9, no. 3: 50. https://doi.org/10.3390/toxics9030050

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