Adverse Effects from Clenbuterol and Ractopamine on Nematode Caenorhabditis elegans and the Underlying Mechanism
Autor: | Lingmei Sun, Haicui Liu, Yunli Zhao, Dayong Wang, Qiuli Wu, Min Li, Gao Wei, Ziheng Zhuang |
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Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
medicine.medical_treatment
Gene Expression Pharmacology AMP-Activated Protein Kinases medicine.disease_cause Toxicology chemistry.chemical_compound Insulin Signaling Cascade Molecular Cell Biology Insulin Intestinal Mucosa Cellular Stress Responses chemistry.chemical_classification Multidisciplinary biology Forkhead Transcription Factors Animal Models Adrenergic beta-Agonists Signaling Cascades Ractopamine DNA-Binding Proteins Intestines Toxicity Medicine Public Health Signal transduction Locomotion Research Article Signal Transduction medicine.medical_specialty Drugs and Devices Science Toxic Agents Longevity Protein Serine-Threonine Kinases Superoxide dismutase Model Organisms Adverse Reactions Somatomedins Internal medicine Phenethylamines medicine Animals Clenbuterol Caenorhabditis elegans Caenorhabditis elegans Proteins Biology Reactive oxygen species Superoxide Dismutase Clutch Size Insulin receptor Oxidative Stress Endocrinology chemistry biology.protein Reactive Oxygen Species Oxidative stress Transcription Factors |
Zdroj: | PLoS ONE PLoS ONE, Vol 9, Iss 1, p e85482 (2014) |
ISSN: | 1932-6203 |
Popis: | 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. |
Databáze: | OpenAIRE |
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