Effects of carbamazepine on the central nervous system of zebrafish at human therapeutic plasma levels

Weiwei Yang; Yifan Bao; Jiaoyang Hao; Xialin Hu; Ting Xu; Daqiang Yin

doi:10.1016/j.isci.2023.107688

Effects of carbamazepine on the central nervous system of zebrafish at human therapeutic plasma levels

iScience. 2023 Aug 23;26(10):107688. doi: 10.1016/j.isci.2023.107688. eCollection 2023 Oct 20.

Authors

Weiwei Yang^{1

2}, Yifan Bao^{1

2}, Jiaoyang Hao^{1

2}, Xialin Hu^{1

2}, Ting Xu^{1

2}, Daqiang Yin^{1

2}

Affiliations

¹ Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tinggi University, Shanghai 200092, China.
² Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, China.

Abstract

The fish plasma model (FPM) facilitated the environmental risk assessment of human drugs by using existing data on human therapeutic plasma concentrations (H_TPCs) and predicted fish plasma concentrations (FPCs). However, studies on carbamazepine (CMZ) with both the mode of action (MOA) based biological effects at molecular level (such as neurotransmitter and gene level) and measured FPCs are lacking. Bioconcentration of CMZ in adult zebrafish demonstrated that the FPM underestimated the bioconcentration factors (BCFs) in plasma at environmental CMZ exposure concentrations (1-100 μg/L). CMZ significantly increased Glu and GABA, decreased ACh and AChE as well as inhibited the transcription levels of gabra1, grin1b, grin2b, gad1b, and abat when the actual FPCs were in the ranges of 1/1000 H_TPC to H_TPC. It is the first read-across study of CMZ integrating MOA-based biological effects at molecular level and FPCs. This study facilitates model performance against a range of different drug classes.

Keywords: Animal physiology; Biochemistry; Biological sciences; Physiology.