{"title":"氧化应激、氧化损伤和细胞凋亡:阿雷科林在秀丽隐杆线虫中诱导的毒性及缓解剂的筛选","authors":"Kaiping Xiang, Bing Wang, Lanying Wang, Yunfei Zhang, Hanzeng Li, Yanping Luo","doi":"10.3390/toxins16080352","DOIUrl":null,"url":null,"abstract":"As the areca nut market is expanding, there is a growing concern regarding areca nut toxicity. Areca nut alkaloids are the major risky components in betel nuts, and their toxic effects are not fully understood. Here, we investigated the parental and transgenerational toxicity of varied doses of areca nut alkaloids in Caenorhabditis elegans. The results showed that the minimal effective concentration of arecoline is 0.2–0.4 mM. First, arecoline exhibited transgenerational toxicity on the worms’ longevity, oviposition, and reproduction. Second, the redox homeostasis of C. elegans was markedly altered under exposure to 0.2–0.4 mM arecoline. The mitochondrial membrane potential was thereafter impaired, which was also associated with the induction of apoptosis. Moreover, antioxidant treatments such as lycopene could significantly ameliorate the toxic effects caused by arecoline. In conclusion, arecoline enhances the ROS levels, inducing neurotoxicity, developmental toxicity, and reproductive toxicity in C. elegans through dysregulated oxidative stress, cell apoptosis, and DNA damage-related gene expression. Therefore, the drug-induced production of reactive oxygen species (ROS) may be crucial for its toxic effects, which could be mitigated by antioxidants.","PeriodicalId":23119,"journal":{"name":"Toxins","volume":null,"pages":null},"PeriodicalIF":3.9000,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Oxidative Stress, Oxidative Damage, and Cell Apoptosis: Toxicity Induced by Arecoline in Caenorhabditis elegans and Screening of Mitigating Agents\",\"authors\":\"Kaiping Xiang, Bing Wang, Lanying Wang, Yunfei Zhang, Hanzeng Li, Yanping Luo\",\"doi\":\"10.3390/toxins16080352\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"As the areca nut market is expanding, there is a growing concern regarding areca nut toxicity. Areca nut alkaloids are the major risky components in betel nuts, and their toxic effects are not fully understood. Here, we investigated the parental and transgenerational toxicity of varied doses of areca nut alkaloids in Caenorhabditis elegans. The results showed that the minimal effective concentration of arecoline is 0.2–0.4 mM. First, arecoline exhibited transgenerational toxicity on the worms’ longevity, oviposition, and reproduction. Second, the redox homeostasis of C. elegans was markedly altered under exposure to 0.2–0.4 mM arecoline. The mitochondrial membrane potential was thereafter impaired, which was also associated with the induction of apoptosis. Moreover, antioxidant treatments such as lycopene could significantly ameliorate the toxic effects caused by arecoline. In conclusion, arecoline enhances the ROS levels, inducing neurotoxicity, developmental toxicity, and reproductive toxicity in C. elegans through dysregulated oxidative stress, cell apoptosis, and DNA damage-related gene expression. Therefore, the drug-induced production of reactive oxygen species (ROS) may be crucial for its toxic effects, which could be mitigated by antioxidants.\",\"PeriodicalId\":23119,\"journal\":{\"name\":\"Toxins\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-08-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Toxins\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3390/toxins16080352\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"FOOD SCIENCE & TECHNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxins","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/toxins16080352","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"FOOD SCIENCE & TECHNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
随着槟榔市场的不断扩大,人们对槟榔的毒性也越来越关注。槟榔生物碱是槟榔中的主要危险成分,其毒性作用尚不完全清楚。在这里,我们研究了不同剂量的槟榔生物碱在秀丽隐杆线虫体内的亲代和转代毒性。结果表明,山苍子碱的最小有效浓度为 0.2-0.4 mM。首先,山苍子碱对草履虫的寿命、产卵和繁殖具有跨代毒性。其次,在暴露于 0.2-0.4 毫摩尔的阿斯高林下,秀丽隐杆线虫的氧化还原平衡发生了显著变化。线粒体膜电位随后受损,这也与诱导细胞凋亡有关。此外,番茄红素等抗氧化剂也能显著改善异胆碱的毒性作用。总之,阿可灵会提高 ROS 水平,通过氧化应激失调、细胞凋亡和 DNA 损伤相关基因表达,诱导秀丽隐杆线虫的神经毒性、发育毒性和生殖毒性。因此,药物诱导的活性氧(ROS)的产生可能是其毒性效应的关键,而抗氧化剂可以减轻这种效应。
Oxidative Stress, Oxidative Damage, and Cell Apoptosis: Toxicity Induced by Arecoline in Caenorhabditis elegans and Screening of Mitigating Agents
As the areca nut market is expanding, there is a growing concern regarding areca nut toxicity. Areca nut alkaloids are the major risky components in betel nuts, and their toxic effects are not fully understood. Here, we investigated the parental and transgenerational toxicity of varied doses of areca nut alkaloids in Caenorhabditis elegans. The results showed that the minimal effective concentration of arecoline is 0.2–0.4 mM. First, arecoline exhibited transgenerational toxicity on the worms’ longevity, oviposition, and reproduction. Second, the redox homeostasis of C. elegans was markedly altered under exposure to 0.2–0.4 mM arecoline. The mitochondrial membrane potential was thereafter impaired, which was also associated with the induction of apoptosis. Moreover, antioxidant treatments such as lycopene could significantly ameliorate the toxic effects caused by arecoline. In conclusion, arecoline enhances the ROS levels, inducing neurotoxicity, developmental toxicity, and reproductive toxicity in C. elegans through dysregulated oxidative stress, cell apoptosis, and DNA damage-related gene expression. Therefore, the drug-induced production of reactive oxygen species (ROS) may be crucial for its toxic effects, which could be mitigated by antioxidants.
期刊介绍:
Toxins (ISSN 2072-6651) is an international, peer-reviewed open access journal which provides an advanced forum for studies related to toxins and toxinology. It publishes reviews, regular research papers and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.