Sulfonamides (SAs) exposure causes neurobehavioral toxicity at environmentally relevant concentrations (ERCs) in early development of zebrafish

作者全名："Huo, Wen-Bo; Jia, Pan-Pan; Li, Wei-Guo; Xie, Xiao-Yu; Yang, Guan; Pei, De-Sheng"

作者地址："[Huo, Wen-Bo; Li, Wei-Guo] Henan Normal Univ, Coll Life Sci, Xinxiang 453007, Peoples R China; [Huo, Wen-Bo; Jia, Pan-Pan; Pei, De-Sheng] Chongqing Med Univ, Sch Publ Hlth, Chongqing 400016, Peoples R China; [Xie, Xiao-Yu] Henan Agr Univ, Coll Vet Med, Zhengzhou 450046, Peoples R China; [Yang, Guan] Chongqing Jiaotong Univ, Environm Sci & Engn, Chongqing 400074, Peoples R China"

通信作者："Pei, DS (通讯作者)，Chongqing Med Univ, Sch Publ Hlth, Chongqing 400016, Peoples R China."

来源：AQUATIC TOXICOLOGY

ESI学科分类：PLANT & ANIMAL SCIENCE

WOS号：WOS:001027020100001

JCR分区：Q1

影响因子：4.1

年份：2023

卷号：261

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Sulfonamides; Developmental toxicity; Neurobehavior; Folic acid metabolism; Carbonic anhydrase metabolism; Zebrafish

摘要："Antibiotics, due to their stability and persistence in the environment, can have chronic impacts on various ecosystems and organisms. However, the molecular mechanisms underlying antibiotic toxicity at environmental concentrations, particularly the neurotoxic effects of sulfonamides (SAs), remain poorly understood. In this study, we assessed the neurotoxicity of six SAs including the sulfadiazine (SD), sulfathiazole (ST), sulfamethoxazole (SMX), sulfisoxazole (SIZ), sulfapyridine (SPD), and sulfadimethoxine (SDM) by exposing zebrafish to environmentally relevant concentrations (ERCs). The SAs exhibited concentration-dependent effects on zebrafish behavior, including spontaneous movement, heartbeat, survival rate, and body metrics, ultimately leading to depressive-like symptoms and sublethal toxicity during early life stages. Notably, even the lowest SA concentration (0.05 & mu;g/L) induced neurotoxicity and behavioral impairment in zebrafish. We observed a dosedependent increase in melancholy behavior as indicated by increased resting time and decreased motor activity in zebrafish larvae. Following exposure to SAs from 4 to 120 h post-fertilization (hpf), key genes involved in folate synthesis [sepiapterin reductase a (spra), phenylalanine hydroxylase (pah), tyrosine hydroxylase (th), and tryptophan hydroxylase 1 (tryptophan 5-monooxygenase) a tryptophan hydroxylase (tph1a)] and carbonic anhydrase (CA) metabolism [carbonic anhydrase II (ca2), carbonic anhydrase IV a (ca4a), carbonic anhydrase VII (ca7), and carbonic anhydrase XIV (ca14)] were significantly downregulated or inhibited at different concentrations. Our findings demonstrate that acute exposure to six SAs at environmentally relevant concentrations induces developmental and neurotoxic effects in zebrafish, impacting folate synthesis pathways and CA metabolism. These results provide valuable insights into the potential role of antibiotics in depressive disorders and neuroregulatory pathways."

基金机构："Chongqing Medical University Talent Project [R4014, R4020]; National Natural Science Foundation of China (NSFC) [32200386]; China-Sri Lanka Joint Research and Demonstration Center for Water Technology, China-Sri Lanka Joint Center for Education and Research, Chinese Academy of Sciences, China"

基金资助正文："This work was supported by Chongqing Medical University Talent Project (No. R4014 to D.S.P., and R4020 to P.P.J.) , National Natural Science Foundation of China (NSFC, No.32200386 to P.P.J) , and China-Sri Lanka Joint Research and Demonstration Center for Water Technology, China-Sri Lanka Joint Center for Education and Research, Chinese Academy of Sciences, China. We really appreciate the editors and reviewers for your valuable comments and suggestions on this study, which help us to improve the manuscript quality."