Adverse effects from clenbuterol and ractopamine on nematode Caenorhabditis elegans and the underlying mechanism.
Adverse effects from clenbuterol and ractopamine on nematode Caenorhabditis elegans and the underlying mechanism.
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DOI：
10.1371/journal.pone.0085482
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Wang D
中科院分区：
文献类型：
--
作者：
Zhuang Z;Zhao Y;Wu Q;Li M;Liu H;Sun L;Gao W;Wang D
在本研究中，我们使用秀丽隐杆线虫检测系统来研究克伦特罗和莱克多巴胺的体内毒性及其可能的机制。急性和长期暴露于克伦特罗或莱克多巴胺降低育雏大小和运动行为，诱导肠道自发荧光和活性氧（ROS）的产生。虽然急性暴露于检测浓度的克伦特洛尔或莱克多巴胺不会导致死亡，但长期暴露于10微克/升的克伦特洛尔和莱克多巴胺会缩短寿命。在较高浓度下，莱克多巴胺对线虫的毒性大于克仑特罗。过表达编码Mn-SOD的sod-2基因以防止氧化应激的诱导，有效地抑制了克仑特罗或莱克多巴胺的毒性。除氧化应激外，我们发现克伦特洛尔可能通过影响胰岛素/IGF信号通路而缩短寿命;而莱克多巴胺可能通过影响胰岛素/IGF信号通路和TOR信号通路而缩短寿命。莱克多巴胺更严重地降低了daf-16，sgk-1，skn-1和aak-2基因的表达水平比克伦特罗，并增加了daf-2和age-1基因的表达水平在检查浓度。因此，C. elegans检测系统可用于评估减肥药可能的毒性，克伦特罗和莱克多巴胺可能通过不同的分子机制诱导毒性。
In the present study, we used Caenorhabditis elegans assay system to investigate in vivo toxicity from clentuberol and ractopamine and the possible underlying mechanism. Both acute and prolonged exposures to clentuberol or ractopamine decreased brood size and locomotion behavior, and induced intestinal autofluorescence and reactive oxygen species (ROS) production. Although acute exposure to the examined concentrations of clentuberol or ractopamine did not induce lethality, prolonged exposure to 10 µg/L of clentuberol and ractopamine reduced lifespan. At relatively high concentrations, ractopamine exhibited more severe toxicity than clentuberol on nematodes. Overexpression of sod-2 gene encoding a Mn-SOD to prevent induction of oxidative stress effectively inhibited toxicity from clentuberol or ractopamine. Besides oxidative stress, we found that clentuberol might reduce lifespan through influencing insulin/IGF signaling pathway; however, ractopamine might reduce lifespan through affecting both insulin/IGF signaling pathway and TOR signaling pathway. Ractopamine more severely decreased expression levels of daf-16, sgk-1, skn-1, and aak-2 genes than clentuberol, and increased expression levels of daf-2 and age-1 genes at the examined concentration. Therefore, the C. elegans assay system may be useful for assessing the possible toxicity from weight loss agents, and clentuberol and ractopamine may induce toxicity through different molecular mechanisms.
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影响因子：
4
作者：
DONKIN, SG;DUSENBERY, DB
通讯作者：
DUSENBERY, DB
影响因子：
4.3
作者：
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通讯作者：
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DOI：
10.1016/j.saa.2012.12.017
发表时间：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
13.6
作者：
Li, Yinxia;Yu, Shunhui;Wang, Dayong
通讯作者：
Wang, Dayong