Adverse effects from clenbuterol and ractopamine on nematode Caenorhabditis elegans and the underlying mechanism.
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.
School of Pharmaceutical Engineering and Life Sciences, Changzhou University, Changzhou, China.
Ziheng
Z
Zhuang
Key Laboratory of Environmental Medicine Engineering in Ministry of Education, Medical School of Southeast University, Nanjing, China.
Yunli
Y
Zhao
Key Laboratory of Environmental Medicine Engineering in Ministry of Education, Medical School of Southeast University, Nanjing, China.
Qiuli
Q
Wu
School of Pharmaceutical Engineering and Life Sciences, Changzhou University, Changzhou, China ; Key Laboratory of Environmental Medicine Engineering in Ministry of Education, Medical School of Southeast University, Nanjing, China.
Min
M
Li
Xiuli Biological Technology Co., Ltd. Changzhou, China.
Haicui
H
Liu
Key Laboratory of Environmental Medicine Engineering in Ministry of Education, Medical School of Southeast University, Nanjing, China.
Lingmei
L
Sun
Jiangsu Province Product Quality Supervision and Inspection Institute, Nanjing, China.
Wei
W
Gao
Key Laboratory of Environmental Medicine Engineering in Ministry of Education, Medical School of Southeast University, Nanjing, China.
Dayong
D
Wang
D055372:AMP-Activated Protein Kinases; D000318:Adrenergic beta-Agonists / Q000633:toxicity*; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002976:Clenbuterol / Q000633:toxicity*; D052284:Clutch Size / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors; D015870:Gene Expression; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects; D008136:Longevity / Q000187:drug effects; D018384:Oxidative Stress; D010627:Phenethylamines / Q000633:toxicity*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction; D013002:Somatomedins / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000099156:Superoxide Dismutase 2
D055372:AMP-Activated Protein Kinases; D000318:Adrenergic beta-Agonists; D029742:Caenorhabditis elegans Proteins; D002976:Clenbuterol; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D007328:Insulin; D010627:Phenethylamines; D017346:Protein Serine-Threonine Kinases; D017382:Reactive Oxygen Species; D013002:Somatomedins; D013482:Superoxide Dismutase; D014157:Transcription Factors; D000099156:Superoxide Dismutase 2; C108831:daf-16 protein, C elegans; C073702:skn-1 protein, C elegans; C060897:ractopamine; C540745:Sgk-1 protein, C elegans; C510541:AAK-2 protein, C elegans