Toxicological effects of atenolol and venlafaxine on zebrafish tissues: Bioaccumulation, DNA hypomethylation, and molecular mechanism

Wenting Lin; Zhishan Huang; Senwen Ping; Shuan Zhang; Xiufang Wen; Yuhe He; Yuan Ren

doi:10.1016/j.envpol.2022.118898

Toxicological effects of atenolol and venlafaxine on zebrafish tissues: Bioaccumulation, DNA hypomethylation, and molecular mechanism

Environ Pollut. 2022 Apr 15:299:118898. doi: 10.1016/j.envpol.2022.118898. Epub 2022 Jan 23.

Authors

Wenting Lin¹, Zhishan Huang¹, Senwen Ping¹, Shuan Zhang², Xiufang Wen², Yuhe He³, Yuan Ren⁴

Affiliations

¹ School of Environment and Energy, South China University of Technology, Guangzhou, 510006, PR China.
² School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510640, PR China.
³ School of Energy and Environment, City University of Hong Kong, Hong Kong, China.
⁴ School of Environment and Energy, South China University of Technology, Guangzhou, 510006, PR China; The Key Lab of Pollution Control and Ecosystem Restoration in Industry Clusters, Ministry of Education, China; The Key Laboratory of Environmental Protection and Eco-Remediation of Guangdong Regular Higher Education Institutions, China. Electronic address: ceyren@scut.edu.cn.

PMID: 35081461
DOI: 10.1016/j.envpol.2022.118898

Abstract

The beta-blocker atenolol (ATE), and the selective serotonin and norepinephrine reuptake inhibitor, venlafaxine (VEN) are frequently detected in municipal wastewater effluents, but little is known about their ecotoxicological effect on aquatic animals. Herein, ATE and VEN were selected to explore their accumulation and global DNA methylation (GDM) in zebrafish tissues after a 30-day exposure. Molecular dynamics (MD) stimulation was used to investigate the toxic mechanism of ATE and VEN exposure. The results demonstrated that ATE and VEN could reduce the condition factor of zebrafish. The bioaccumulation capacity for ATE and VEN was in the order of liver > gut > gill > brain and liver > gut > brain > gill, respectively. After a 30-day recovery, ATE and VEN could still be detected in zebrafish tissues when exposure concentrations were ≥10 μg/L. Moreover, ATE and VEN induced global DNA hypomethylation in different tissues with a dose-dependent manner and their main target tissues were liver and brain. When the exposure concentrations of ATE and VEN were increased to 100 μg/L, the global DNA hypomethylation of liver and brain were reduced to 27% and 18%, respectively. In the same tissue exposed to the same concentration, DNA hypomethylation induced by VEN was more serious than that of ATE. After a 30-day recovery, the global DNA hypomethylations caused by the two drugs were still persistent, and the recovery of VEN was slower than that of ATE. The MD simulation results showed that both ATE and VEN could reduce the catalytic activity of DNA Methyltransferase 1 (DNMT1), while the effect of VEN on the 3D conformational changes of the DNMT1 domain was more significant, resulting in a lower DNA methylation rate. The current study shed new light on the toxic mechanism and potential adverse impacts of ATE and VEN on zebrafish, providing essential information to the further ecotoxicological risk assessment of these drugs in the aquatic environment.

Keywords: Bioaccumulation; DNA hypomethylation; DNMT1; Molecular dynamics simulation; Zebrafish.

MeSH terms

Animals
Atenolol*
Bioaccumulation
DNA
DNA Methylation
Venlafaxine Hydrochloride / toxicity
Zebrafish*

Substances

Atenolol
Venlafaxine Hydrochloride
DNA