Liyan Xu , Yuxin Shi , Jing Huang , Lixin Feng , Yuxin Wang , Attila Gabor SIK , Xiqiang Chen , Kechun Liu , Rongchun Wang , Meng Jin
{"title":"黄嘌呤对斑马鱼胚胎的发育毒性试验。","authors":"Liyan Xu , Yuxin Shi , Jing Huang , Lixin Feng , Yuxin Wang , Attila Gabor SIK , Xiqiang Chen , Kechun Liu , Rongchun Wang , Meng Jin","doi":"10.1016/j.cbpc.2024.109957","DOIUrl":null,"url":null,"abstract":"<div><p>Xanthatin (XAN), a xanthanolide sesquiterpene lactone, isolated from Chinese herb, <em>Xanthium strumarium L</em>, has various pharmacological activities, such as antitumor activity and anti-inflammatory. However, little is known about its potential toxicity and the mechanism. Here, zebrafish model was used to study the developmental toxicity <em>in vivo</em>. Our results indicated that xanthatin increased the mortality and led to the morphological abnormalities including pericardial edema, yolk sac edema, curved body shape and hatching delay. Furthermore, xanthatin damaged the normal structure and/or function of heart, liver, immune and nervous system. ROS elevation and much more apoptosis cells were observed after xanthatin exposure. Gene expression results showed that oxidative stress-related genes <em>nrf2</em> was inhibited, while oxidative stress-related genes (<em>keap1</em> and <em>nqo1</em>) and apoptotic genes (<em>caspase3</em>, <em>caspase9</em> and <em>p53</em>) were increased after xanthatin exposure. Mitophagy related genes <em>pink1</em> and <em>parkin</em>, and wnt pathway (<em>β-catenin</em>, <em>wnt8a</em> and <em>wnt11</em>) were significantly increased after xanthatin exposure. Taken together, our finding indicated that xanthatin induced developmental toxicity, and the ROS elevation, apoptosis activation, dysregulation of mitophagy and wnt pathways were involved in the toxicity caused by xanthatin.</p></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.9000,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Developmental toxicity assay of xanthatin in zebrafish embryos\",\"authors\":\"Liyan Xu , Yuxin Shi , Jing Huang , Lixin Feng , Yuxin Wang , Attila Gabor SIK , Xiqiang Chen , Kechun Liu , Rongchun Wang , Meng Jin\",\"doi\":\"10.1016/j.cbpc.2024.109957\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Xanthatin (XAN), a xanthanolide sesquiterpene lactone, isolated from Chinese herb, <em>Xanthium strumarium L</em>, has various pharmacological activities, such as antitumor activity and anti-inflammatory. However, little is known about its potential toxicity and the mechanism. Here, zebrafish model was used to study the developmental toxicity <em>in vivo</em>. Our results indicated that xanthatin increased the mortality and led to the morphological abnormalities including pericardial edema, yolk sac edema, curved body shape and hatching delay. Furthermore, xanthatin damaged the normal structure and/or function of heart, liver, immune and nervous system. ROS elevation and much more apoptosis cells were observed after xanthatin exposure. Gene expression results showed that oxidative stress-related genes <em>nrf2</em> was inhibited, while oxidative stress-related genes (<em>keap1</em> and <em>nqo1</em>) and apoptotic genes (<em>caspase3</em>, <em>caspase9</em> and <em>p53</em>) were increased after xanthatin exposure. Mitophagy related genes <em>pink1</em> and <em>parkin</em>, and wnt pathway (<em>β-catenin</em>, <em>wnt8a</em> and <em>wnt11</em>) were significantly increased after xanthatin exposure. Taken together, our finding indicated that xanthatin induced developmental toxicity, and the ROS elevation, apoptosis activation, dysregulation of mitophagy and wnt pathways were involved in the toxicity caused by xanthatin.</p></div>\",\"PeriodicalId\":10602,\"journal\":{\"name\":\"Comparative Biochemistry and Physiology C-toxicology & Pharmacology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-06-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Comparative Biochemistry and Physiology C-toxicology & Pharmacology\",\"FirstCategoryId\":\"93\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S153204562400125X\",\"RegionNum\":3,\"RegionCategory\":\"环境科学与生态学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","FirstCategoryId":"93","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S153204562400125X","RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Developmental toxicity assay of xanthatin in zebrafish embryos
Xanthatin (XAN), a xanthanolide sesquiterpene lactone, isolated from Chinese herb, Xanthium strumarium L, has various pharmacological activities, such as antitumor activity and anti-inflammatory. However, little is known about its potential toxicity and the mechanism. Here, zebrafish model was used to study the developmental toxicity in vivo. Our results indicated that xanthatin increased the mortality and led to the morphological abnormalities including pericardial edema, yolk sac edema, curved body shape and hatching delay. Furthermore, xanthatin damaged the normal structure and/or function of heart, liver, immune and nervous system. ROS elevation and much more apoptosis cells were observed after xanthatin exposure. Gene expression results showed that oxidative stress-related genes nrf2 was inhibited, while oxidative stress-related genes (keap1 and nqo1) and apoptotic genes (caspase3, caspase9 and p53) were increased after xanthatin exposure. Mitophagy related genes pink1 and parkin, and wnt pathway (β-catenin, wnt8a and wnt11) were significantly increased after xanthatin exposure. Taken together, our finding indicated that xanthatin induced developmental toxicity, and the ROS elevation, apoptosis activation, dysregulation of mitophagy and wnt pathways were involved in the toxicity caused by xanthatin.
期刊介绍:
Part C: Toxicology and Pharmacology. This journal is concerned with chemical and drug action at different levels of organization, biotransformation of xenobiotics, mechanisms of toxicity, including reactive oxygen species and carcinogenesis, endocrine disruptors, natural products chemistry, and signal transduction with a molecular approach to these fields.