Oxidative Stress and Endoplasmic Reticulum Stress Contributes to Arecoline and Its Secondary Metabolites-Induced Dyskinesia in Zebrafish Embryos

作者全名："Yan, Wenhua; Zhang, Tian; Li, Shuaiting; Wang, Yunpeng; Zhu, Li; Cao, Yu; Lai, Xiaofang; Huang, Huizhe"

作者地址："[Yan, Wenhua; Li, Shuaiting; Wang, Yunpeng; Huang, Huizhe] Chongqing Med Univ, Affiliated Hosp 2, 76 Linjiang Rd, Chongqing 400010, Peoples R China; [Zhang, Tian; Zhu, Li; Cao, Yu] Chongqing Univ, Bioengn Coll, Key Lab Biorheol Sci & Technol, State & Local Joint Engn Lab Vasc Implants, 174 Shazhengjie, Chongqing 400044, Peoples R China; [Lai, Xiaofang] Jiangsu Ocean Univ, Coll Marine Sci & Fisheries, Key Lab Marine Biol Resources & Environm Jiangsu P, Lianyungang 222005, Peoples R China"

通信作者："Huang, HZ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, 76 Linjiang Rd, Chongqing 400010, Peoples R China."

来源：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

ESI学科分类：CHEMISTRY

WOS号：WOS:000969133300001

JCR分区：Q2

影响因子：5.6

年份：2023

卷号：24

期号：7

开始页：　

结束页：　

文献类型：Article

关键词：arecoline; arecaidine; arecoline N-oxide; oxidative stress; endoplasmic reticulum stress; dyskinesia

摘要："Areca nut has been listed as one of the most addictive substances, along with tobacco, alcohol and caffeine. Areca nut contains seven psychoactive alkaloids; however, the effects of these alkaloids on embryonic development and motor behavior are rarely addressed in zebrafish embryo-larvae. Herein, we investigated the effects of exposure to three alkaloids (arecoline and secondary metabolites-arecaidine and arecoline N-oxide) on the developmental parameters, locomotive behavior, oxidative stress and transcriptome of zebrafish embryos. Zebrafish embryos exposed to different concentrations (0, 0.1, 1, 10, 100 and 1000 mu M) of arecoline, arecaidine and arecoline N-oxide showed no changes in mortality and hatchability rates, but the malformation rate of zebrafish larvae was significantly increased in a dose-dependent manner and accompanied by changes in body length. Moreover, the swimming activity of zebrafish larvae decreased, which may be due to the increase in reactive oxygen species and the imbalance between oxidation and antioxidation. Meanwhile, transcriptome analysis showed that endoplasmic reticulum stress and the apoptosis p53 signaling pathway were significantly enriched after exposure to arecoline and arecoline N-oxide. However, arecaidine exposure focuses on protein synthesis and transport. These findings provide an important reference for risk assessment and early warning of areca nut alkaloid exposure."

基金机构："National Natural Science Foundation of China [31771619]; China Postdoctoral Science Foundation [2022MD713708]; Natural Science Foundation of Chongqing, China [cstc2021jcyj-bsh-X0069]"

基金资助正文："This work was supported by the National Natural Science Foundation of China (No. 31771619, to H.H.), the China Postdoctoral Science Foundation (No. 2022MD713708, to W.Y.) and the Natural Science Foundation of Chongqing, China (No. cstc2021jcyj-bsh-X0069, to W.Y.)."