Preliminary study on the role of aryl hydrocarbon receptor in the neurotoxicity of three typical bisphenol compounds (BPA, BPS and TBBPA) at environmentally relevant concentrations to adult zebrafish (Danio rerio)

Jing Shan; Xiao-Fa Ma; Meng-Yu Wu; Yu-Jia Lin; Yi Wang; Rui Wang; Hong-Mei Li; Zhong-Lan Wu; Hai-Ming Xu

doi:10.1016/j.heliyon.2023.e16649

Preliminary study on the role of aryl hydrocarbon receptor in the neurotoxicity of three typical bisphenol compounds (BPA, BPS and TBBPA) at environmentally relevant concentrations to adult zebrafish (Danio rerio)

Heliyon. 2023 May 26;9(6):e16649. doi: 10.1016/j.heliyon.2023.e16649. eCollection 2023 Jun.

Authors

Jing Shan^{1

2}, Xiao-Fa Ma^{1

2}, Meng-Yu Wu^{1

2}, Yu-Jia Lin^{1

2}, Yi Wang^{1

2}, Rui Wang^{1

2}, Hong-Mei Li^{3

4}, Zhong-Lan Wu^{1

5}, Hai-Ming Xu^{1

2}

Affiliations

¹ School of Public Health and Management, Ningxia Medical University, Yinchuan, 750004, Ningxia, China.
² The Key Laboratory of Environmental Factors and Chronic Disease Control of Ningxia, Yinchuan, 750004, Ningxia, China.
³ The Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, 750004, Ningxia, China.
⁴ School of Basic Medicine, Ningxia Medical University, Yinchuan, 750004, Ningxia, China.
⁵ Ningxia Center for Disease Control and Prevention, Yinchuan, 750004, Ningxia, China.

Abstract

Objective: This study was aimed to explore the role of AhR in the neurotoxicity of adult zebrafish induced by three typical bisphenol compounds (BPA, BPS, TBBPA) at environmentally relevant doses.

Methods: The adult zebrafish were randomly divided into solvent control group (DMSO) and AhR inhibitor CH223191 (CH) group (0.05 μmol/L), bisphenol exposure groups (10, 100, 1000 nmol/L) and combined exposure groups (0.05 μmol/L CH and 1000 nmol/L bisphenol compounds). Each tank contained 8 fish (4 male and 4 female), and two parallel tanks were set synchronously. After 30 days of exposure, zebrafish were put on ice plate for anesthesia, weighed and measured for body length, and dissected for brain tissue. The gene expression was detected by RT-qPCR, and the activities of antioxidant enzymes were detected by commercial kits. SPSS 26.0 was used to analyze the data. Additionally, GO, KEGG and principal component analysis (PCA) were carried out.

Results: Compared with the solvent control group, there were no significant differences in body weight and length among the exposed groups. In general, exposure to bisphenol compounds could affect the expression of Ahr2 and AhR target genes (cyp1a1, cyp1a2, and cyp1c1), key genes of neural function (elavl3, gfap, mbp, syn2a, gap43, Zn5, shha, and ache), oxidative stress related genes (nrf2, gpx1a, gstp1/gstp1.2, gstp2/gstp1.1, sod1, sod2, and cat), and the activities of antioxidant enzymes (SOD, CAT and GSH-Px/GPX) in zebrafish brain tissue to some extent. Compared with the groups exposed to bisphenols alone, CH could antagonize the above interference effects caused by bisphenols to some extent. Therefore, the toxic effects of BPA, BPS and TBBPA might be produced through similar mechanisms.

Conclusion: Environmentally related doses of bisphenols (BPA, BPS, TBBPA) could disturb the expression of key molecules of oxidative stress and neural function through activating the AhR signaling pathway, and ultimately lead to neurotoxicity.

Keywords: Aryl hydrocarbon receptor; Bisphenol compounds; Environmentally relevant concentrations; Neurotoxicity; Zebrafish.