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
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