ABSTRACT
A high-performance liquid chromatography method employing a diode-array detector and mass spectrometry detector was developed, validated and implemented for determining Synephrine, Caffeine, Clenbuterol, Nandrolone, Testosterone and Methylhexaneamine in Nutritional supplements. The use of Nutritional supplements is widespread. Hazards relating to concentration, composition, individual contaminants, supplements interactions as well as positive doping results among athletes present increasing concerns regarding nutritional supplement consuming. The proposed method was validated according to the International Conference on the Harmonization of the Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) standards. The proposed method observed to be accurate, linear, precise, sensitive, required minimal sample preparation and uncomplicated mobile phase. The implementation of the proposed method on nine commercial supplements shows that inaccurate labeling for some supplements regarding the concentration of the ingredients.
Subject(s)
Chromatography, High Pressure Liquid/methods , Dietary Supplements/analysis , Mass Spectrometry/methods , Testosterone Congeners/analysis , Amines/analysis , Caffeine/analysis , Central Nervous System Stimulants/analysis , Chromatography, Liquid/methods , Clenbuterol/analysis , Nandrolone/analysis , Reproducibility of Results , Synephrine/analysisABSTRACT
A series of phosphorene (BP) nanocomposites was prepared to realize simultaneous electrochemical determination of clenbuterol (CLB) and ractopamine (RAC). CLB and RAC are the most commonly used ß-agonists in animal-derived food. The BP nanohybrid was obtained by co-decoration with both mono(6-mercapto-6-deoxy)-ß-cyclodextrin and poly(3,4-ethylenedioxythiophene) nanoparticles. It displays high stability, antifouling capability, a large electrochemical active surface and good electrochemical response. The electrochemical assisted antifouling strategy was selected by further eliminating the fouling of the electrode surface using continuous cyclic voltammetry. The electrode was employed for electrochemical sensing of CLB and RAC at typical peak voltages of 0.8 and 1.0 V (vs. SCE). Responses are linear in the 0.3-90 µM concentration range for CLB, and from 0.3 to 9.4 µM for RAC under optimal conditions. The limit of detection are 0.14 and 0.12 µM, respectively. The sensor was employed for simultaneous determination of CLB and RAC in (spiked) beef, feed and bovine serum samples with acceptable recoveries. Graphical abstractAn electrochemically assisted anti-fouling method for simultaneous voltammetric nanosensing of clenbuterol (CLB) and ractopamine (RAC) in edible cattle product samples using high-stable and anti-foul phosphorene (BP) co-decorated with mono(6-mercapto-6-deoxy)-ß-cyclodextrin (S-ß-CD) and poly(3,4-ethylenedioxythiophene) (PEDOTNPs).
Subject(s)
Biofouling/prevention & control , Clenbuterol/analysis , Nanocomposites/chemistry , Phenethylamines/analysis , Phosphorus/chemistry , Animals , Cattle , Electrochemical Techniques , Electrodes , Particle Size , Surface PropertiesABSTRACT
A visualization strategy is described for the detection of clenbuterol (CLB). It is using of antibody against dsDNA and G-quadruplex/hemin labeled on a metal organic framework of type MIL-101(Fe) (G-quadruplex/hemin-anti-DNA/MIL-101) acting as a peroxidase mimetic, and magnetic beads modified with aptamer and complementary DNA (MB/Apt-cDNA) as capture probes. The detection reagent was prepared via the reactions between the double stranded DNA (Apt-cDNA) in capture probes and anti-DNA in peroxidase mimetic. In the presence of CLB, the aptamer on the magnetic beads preferentially binds CLB, and the peroxidase mimetic is released to the supernatant after magnetic separation. The released peroxidase mimetic can catalyze the TMB/H2O2 chromogenic system under mild conditions. This leads to the development of a blue-green coloration whose absorbance is measured at 650 nm. The detection limit is as low as 34 fM of CLB. The method was applied to the determination of CLB in pork samples and gave results that were consistent with data obtained with an ELISA kit. Graphical abstract A visualization strategy is described for the detection of clenbuterol. The selectivity of detection system for clenbuterol is excellent compared with other interferents. The method was applied to the determination of CLB in pork samples.
Subject(s)
Adrenergic beta-Agonists/analysis , Clenbuterol/analysis , Food Contamination/analysis , Red Meat/analysis , Swine , Adrenergic beta-Agonists/chemistry , Animals , Antibodies/chemistry , Aptamers, Nucleotide/chemistry , Biomimetics , Clenbuterol/chemistry , Colorimetry , DNA/chemistry , DNA/immunology , G-Quadruplexes , Hemin/chemistry , Iron/chemistry , Magnetic Phenomena , Metal-Organic Frameworks/chemistry , Peroxidase/chemistryABSTRACT
AIM: To investigate whether electroacupuncture (EA) at ST25 affects jejunal motility in vivo and if so, whether a sympathetic pathway is involved. METHODS: Jejunal motility was assessed using a manometric balloon placed in the jejunum approximately about 3-5 cm away from the suspensory ligament of the duodenum in anesthetized animals. The effects of EA at ST25 were measured in male Sprague-Dawley rats, some of which were treated with propranolol or clenbuterol (EA intensities: 1, 3, 5, 7, and 9 mA), and in male transient receptor potential vanilloid-1 (TRPV1) (capsaicin receptor) knockout mice (EA intensities: 1, 2, and 4 mA). RESULTS: Anesthetized rats exhibited three types of fasting jejunal motor patterns (types A, B, and C), and only type C rats responded to EA stimulation. In type C rats, EA at ST25 significantly suppressed the motor activity of the jejunum in an intensity-dependent manner. The inhibitory effect of EA was weakened by propranolol (ß adrenoceptor antagonist) and disappeared with clenbuterol (ß adrenoceptor agonist) induced inhibition of motility, suggesting that the effect of EA on motility is mediated via a sympathetic pathway. Compared with wild-type mice, EA at ST25 was less effective in TRPV1 knockout mice, suggesting that this multi-modal sensor channel participates in the mechanism. CONCLUSION: EA at ST25 was found to inhibit jejunal motility in an intensity-dependent manner, via a mechanism in which sympathetic nerves and TRPV1 receptors play an important role.
Subject(s)
Acupuncture Points , Electroacupuncture/methods , Gastrointestinal Motility , Jejunum/innervation , Sympathetic Nervous System/metabolism , TRPV Cation Channels/metabolism , Adrenergic beta-Agonists/pharmacology , Adrenergic beta-Antagonists/pharmacology , Animals , Clenbuterol/pharmacology , Gastrointestinal Motility/drug effects , Genotype , Male , Mice, Knockout , Motor Activity , Phenotype , Propranolol/pharmacology , Rats, Sprague-Dawley , Reflex , Sympathetic Nervous System/drug effects , TRPV Cation Channels/deficiency , TRPV Cation Channels/genetics , Time FactorsABSTRACT
P-glycoprotein (P-gp)-mediated drug-drug interactions are important factors causing adverse effects of drugs in clinical use. The aim of this study was to determine whether trantinterol (also known as SPFF), a novel ß2-adrenoceptor agonist, was a P-gp inhibitor or substrate. The results showed that trantinterol was not a substrate of P-gp but increased rhodamine 123 (Rho 123) uptake by MDCK-MDR1 cells and decreased the efflux transport of both Rho 123 and cyclosporine A (CsA) in bidirectional transport studies across MDCK-MDR1 cell monolayers. This suggested that trantinterol was a P-gp inhibitor but not a P-gp substrate. The mechanism of inhibition was investigated in the P-gp-Glo assay system, where it was found that trantinterol inhibited P-gp ATPase activity in a dose-dependent manner. A subsequent study using the antibody binding assay with the conformation-sensitive P-gp-specific antibody UIC2 confirmed that trantinterol decreased UIC2 binding at 10 µM in contrast to the competitive inhibitor, verapamil. This suggested that trantinterol was a noncompetitive inhibitor of P-gp. Finally, a pharmacokinetic study in rat showed that trantinterol significantly increased the area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax) of digoxin and paclitaxel (PAC), and the Cmax of cyclosporine A (CsA). In summary, trantinterol is a potent noncompetitive P-gp inhibitor which may increase the bioavailability of other P-gp substrate drugs coadministered with it.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors , Adrenergic beta-Agonists/chemistry , Clenbuterol/analogs & derivatives , Adenosine Triphosphatases/chemistry , Animals , Antibodies, Monoclonal/chemistry , Area Under Curve , Binding Sites , Biological Transport , Caco-2 Cells , Clenbuterol/chemistry , Cyclosporine/chemistry , Digoxin/chemistry , Dogs , Drug Evaluation, Preclinical , Humans , Madin Darby Canine Kidney Cells , Male , Paclitaxel/chemistry , Rats , Rats, Wistar , Rhodamine 123/chemistryABSTRACT
OBJECTIVE: To observe the effect of three Chinese medical formulae (Zhifei Mixture I , Zhfei Mixture II, and Zhifei Mixture II) on main and secondary symptoms and signs of children with Totally 70 mycoplasma pneumonia in treating three types of children mycoplasma pneumonia. METHODS: children with mycoplasma pneumonia were assigned to the control group (38 cases) and the treatment group (32 case). All patients were intravenously injected with Azithromycin and took Ambroxol Hydrochloride and Clenbuterol Hydrochloride Oral Solution. Those in the treatment group additionally took Zhifei Mixture I , Zhfei Mixture II, and Zhifei Mixture Ill by syndrome typing. Their main and secondary symptoms and signs were observed before and after treatment (main symptoms and signs covered fever, cough, abundant sputum, short breath, and anoxia; secondary symptoms and signs covered aversion to cold, heart rate, facial complexion, spirit, appetite, and sweating). RESULTS: Seven patients were lost in this study. Compared with before treatment in the same group, scores for main and secondary symptoms and signs decreased in the treatment group (P <0.01). The therapeutic effect on fever and cough was obviously better in the control group (P <0.01). The main and secondary symptoms and signs were more obviously improved in the treatment group than in the control group (P <0.01). Commpared with the control group, scores for main and secondary symptoms and signs decreased more in the treatment group (P <0.01). Patients' main and secondary symptoms and signs were more obviously improved (P <0.05). CONCLUSIONS: Zhifei Mixture combined Western drugs could significantly improve main and secondary symptoms and signs of mycoplasma pneumonia children patients. Its efficacy was superior to that of using Western medicine alone.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Pneumonia, Mycoplasma/drug therapy , Ambroxol/administration & dosage , Ambroxol/therapeutic use , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Azithromycin/administration & dosage , Azithromycin/therapeutic use , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/therapeutic use , Child , Clenbuterol/administration & dosage , Clenbuterol/therapeutic use , Expectorants/administration & dosage , Expectorants/therapeutic use , Fever , Humans , SyndromeABSTRACT
<p><b>OBJECTIVE</b>To observe the effect of three Chinese medical formulae (Zhifei Mixture I , Zhfei Mixture II, and Zhifei Mixture II) on main and secondary symptoms and signs of children with Totally 70 mycoplasma pneumonia in treating three types of children mycoplasma pneumonia.</p><p><b>METHODS</b>children with mycoplasma pneumonia were assigned to the control group (38 cases) and the treatment group (32 case). All patients were intravenously injected with Azithromycin and took Ambroxol Hydrochloride and Clenbuterol Hydrochloride Oral Solution. Those in the treatment group additionally took Zhifei Mixture I , Zhfei Mixture II, and Zhifei Mixture Ill by syndrome typing. Their main and secondary symptoms and signs were observed before and after treatment (main symptoms and signs covered fever, cough, abundant sputum, short breath, and anoxia; secondary symptoms and signs covered aversion to cold, heart rate, facial complexion, spirit, appetite, and sweating).</p><p><b>RESULTS</b>Seven patients were lost in this study. Compared with before treatment in the same group, scores for main and secondary symptoms and signs decreased in the treatment group (P <0.01). The therapeutic effect on fever and cough was obviously better in the control group (P <0.01). The main and secondary symptoms and signs were more obviously improved in the treatment group than in the control group (P <0.01). Commpared with the control group, scores for main and secondary symptoms and signs decreased more in the treatment group (P <0.01). Patients' main and secondary symptoms and signs were more obviously improved (P <0.05).</p><p><b>CONCLUSIONS</b>Zhifei Mixture combined Western drugs could significantly improve main and secondary symptoms and signs of mycoplasma pneumonia children patients. Its efficacy was superior to that of using Western medicine alone.</p>
Subject(s)
Child , Humans , Ambroxol , Therapeutic Uses , Anti-Bacterial Agents , Therapeutic Uses , Azithromycin , Therapeutic Uses , Bronchodilator Agents , Therapeutic Uses , Clenbuterol , Therapeutic Uses , Drugs, Chinese Herbal , Therapeutic Uses , Expectorants , Therapeutic Uses , Fever , Pneumonia, Mycoplasma , Drug Therapy , SyndromeABSTRACT
OBJECTIVE: To study clinical features, treatment and curative effects in children with acute clenbuterol poisoning, in order to provide a basis for early diagnosis and treatment. METHODS: Clinical data of 28 hospitalized children with acute clenbuterol poisoning in April 2011 were retrospectively studied. RESULTS: Of the 28 patients, there were 15 males and 13 females, aged 1 to 13 years (mean age 6.5±4.8 years). Vomiting, palpitations and limb shaking were found as main clinical manifestations in the patients. Main changes of blood biochemical included hypokalemia, lactic acidosis, hyperglycemia, hypsocreatinkinase. Snus tachycardia and S-T segment depression were observed on ECG. Patients' symptoms were gradually alleviated after 12-78 hours by use of beta blockers, potassium supplement, protecting the heart and other symptomatic and supportive treatment. Blood biochemical indexes were improved after 48 hours of admission. All of the patients were cured after 5 days. The symptoms of the patients do not longer occur during a follow up of half a month. CONCLUSIONS: Acute clenbuterol poisoning is characterized by vomiting, palpitations, limb shaking, hypokalemia, lactic acidosis and tachycardia in children. An early effective treatment of this disease can improve prognosis in children.
Subject(s)
Adrenergic beta-Agonists/poisoning , Clenbuterol/poisoning , Acute Disease , Adolescent , Child , Child, Preschool , Electrocardiography , Female , Humans , Infant , Male , Retrospective StudiesABSTRACT
INTRODUCTION. Anabolic-androgenic steroids are synthetic substances derived from testosterone that are employed for their trophic effect on muscle tissue, among other uses. Their consumption can give trigger a series of adverse side effects on the body, including the suppression of the hypothalamus-pituitary-gonadal axis as well as liver, psychiatric and cardiovascular disorders. The most common effects are altered fat profiles and blood pressure values, cardiac remodelling, arrhythmias or myocardial infarcts. CASE REPORT. We report the case of a young male, with a background of anabolic-androgenic steroids abuse, who visited because of an acute neurological focus in the right hemisphere related with an ischaemic stroke. The aetiological study, including cardiac monitoring, echocardiograph and imaging studies (magnetic resonance and arteriography) and lab findings (thrombophilia, serology, autoimmunity, tumour markers) showed no alterations. CONCLUSIONS. The association between consumption of anabolic-androgenic steroids and cardiovascular pathologies is known, but its relation with cerebrovascular disease has not received so much attention from researchers.
Subject(s)
Anabolic Agents/adverse effects , Doping in Sports , Infarction, Middle Cerebral Artery/chemically induced , Steroids/adverse effects , Substance-Related Disorders/complications , Adult , Alcoholism/complications , Brain Ischemia/chemically induced , Cerebral Angiography , Clenbuterol/adverse effects , Fibrinolytic Agents/therapeutic use , Humans , Infarction, Middle Cerebral Artery/diagnostic imaging , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/therapy , Male , Martial Arts , Mechanical Thrombolysis , Naltrexone/therapeutic use , Nandrolone/adverse effects , Nandrolone/analogs & derivatives , Nandrolone Decanoate , Stanozolol/adverse effects , Substance-Related Disorders/drug therapy , Testosterone Propionate/adverse effects , Tissue Plasminogen Activator/therapeutic use , Tomography, X-Ray ComputedABSTRACT
<p><b>OBJECTIVE</b>To study clinical features, treatment and curative effects in children with acute clenbuterol poisoning, in order to provide a basis for early diagnosis and treatment.</p><p><b>METHODS</b>Clinical data of 28 hospitalized children with acute clenbuterol poisoning in April 2011 were retrospectively studied.</p><p><b>RESULTS</b>Of the 28 patients, there were 15 males and 13 females, aged 1 to 13 years (mean age 6.5±4.8 years). Vomiting, palpitations and limb shaking were found as main clinical manifestations in the patients. Main changes of blood biochemical included hypokalemia, lactic acidosis, hyperglycemia, hypsocreatinkinase. Snus tachycardia and S-T segment depression were observed on ECG. Patients' symptoms were gradually alleviated after 12-78 hours by use of beta blockers, potassium supplement, protecting the heart and other symptomatic and supportive treatment. Blood biochemical indexes were improved after 48 hours of admission. All of the patients were cured after 5 days. The symptoms of the patients do not longer occur during a follow up of half a month.</p><p><b>CONCLUSIONS</b>Acute clenbuterol poisoning is characterized by vomiting, palpitations, limb shaking, hypokalemia, lactic acidosis and tachycardia in children. An early effective treatment of this disease can improve prognosis in children.</p>
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Acute Disease , Adrenergic beta-Agonists , Poisoning , Clenbuterol , Poisoning , Electrocardiography , Retrospective StudiesABSTRACT
The aim of this study was to determine the level of clenbuterol residues in muscle tissue of pigs after repeat administration in a growth-promoting dose. An anabolic dose of clenbuterol (20 µg/kg body mass per day) was administered orally to experimental group (n=12) for 28 days, whereas control animals (n=3) were left untreated. Clenbuterol treated pigs were randomly sacrificed (n=3) on days 0, 3, 7 and 14 of treatment discontinuation and clenbuterol residues determined in muscle tissue. Determination of residual clenbuterol was by enzyme-linked immunosorbent assay (ELISA) as a screening method and liquid chromatography tandem mass spectrometry (LC-MS/MS) as a confirmation method. The highest clenbuterol content in the muscle of treated animals was recorded on day 0 of treatment cessation (4.40±0.37 ng/g) and significantly (p<0.05) exceeded the maximum residue limit (MRL) of 0.1 ng/g. On day 3 of withdrawal, it was 0.49±0.22 ng/g and on day 7 0.10±0.02 ng/g (at MRL); on day 14 of treatment discontinuation, clenbuterol content was below the limit of detection (<0.1 ng/g) in all samples. Administration of clenbuterol as a growth promoter in pig production could lead to residues in meat for human consumption up to 7 days after treatment discontinuation.
Subject(s)
Adrenergic beta-Agonists/analysis , Anabolic Agents/analysis , Clenbuterol/analysis , Drug Residues/analysis , Food Contamination/analysis , Meat/analysis , Adrenergic beta-Agonists/administration & dosage , Anabolic Agents/administration & dosage , Animals , Chromatography, Liquid , Clenbuterol/administration & dosage , Dietary Supplements , Enzyme-Linked Immunosorbent Assay , Humans , Limit of Detection , Male , Muscle, Skeletal/chemistry , Swine , Tandem Mass SpectrometryABSTRACT
In several studies it has been demonstrated that products containing pharmaceutically active ingredients are marketed as dietary supplements. Most of these products contain anabolic steroids. Recently products for weight loss containing active drugs have also appeared on the market. In the present case a healthy male ordered the product 'Anabolic burner' via the Internet. The product was received from a German dispatcher and paid by bank transfer to a German bank account. After ingesting one tablet he reported tremor and delivered a urine sample. This urine was found to contain 2 ng/mL of clenbuterol utilizing LC-MS/MS analysis. Additionally the product itself was analyzed with GC-MS for clenbuterol, yielding a content of about 30 microg per tablet. The beta-2 agonist clenbuterol is only legally available on prescription and is classified as prohibited doping substance in sports. The present case for the first time confirms the presence of clenbuterol in a dietary supplement. It again demonstrates the common problem with products on the supplement market, where non-licensed pharmaceuticals and doping substances are easily available. The ingestion of these products containing additions of therapeutic drugs can lead to side effects and/or interactions with conventional medicines.
Subject(s)
Clenbuterol/adverse effects , Dietary Supplements , Chromatography, Liquid , Clenbuterol/urine , Gas Chromatography-Mass Spectrometry , Humans , Male , Tandem Mass SpectrometryABSTRACT
beta2-Adrenergic agonists (BAAs) act as repartitioning agents in domestic animals by redistributing nutrients away from adipose tissue and towards muscle accretion. The mechanism involves altering the rates of protein degradation and synthesis. The aim of this study was to test the effects of chronic feeding of the BAAs clenbuterol (CLEN) and ractopamine (RACT) on rainbow trout (RBT) muscle. Specifically, we examined the activities and mRNA levels of genes in the major proteolytic pathways including calpains, the multi-catalytic proteasome and cathepsins, and the mRNA levels of genes encoding the myofibrillar proteins, fast-twitch and slow-twitch myosin heavy chains (f-MHC and s-MHC, respectively), and the cytoskeletal protein, beta-actin. RACT feeding significantly increased mRNA transcripts of the calpain catalytic subunit (Capn1), the regulatory subunit (cpns), and the calpastatin large isoform (CAST-L), without affecting the calpain enzyme activity. CLEN feeding significantly increased mRNA levels of the proteasome alpha subunit without a corresponding change in 20S enzyme activity. RACT significantly decreased cathepsin D activity without affecting mRNA levels suggesting that the action of RACT may be at the post-transcriptional level. In addition, both CLEN and RACT significantly increased mRNA transcripts of f-MHC and beta-actin genes suggesting an anabolic role of BAAs on myofibrillar and cytoskeletal proteins. Neither CLEN nor RACT altered mRNA expression of the s-MHC gene indicating no transformation of muscle fiber-types. This study supports a role for BAAs in inducing RBT muscle accretion by altering both protein synthesis and degradation.
Subject(s)
Adrenergic beta-Agonists/adverse effects , Muscle Proteins/metabolism , Muscles/drug effects , Oncorhynchus mykiss/metabolism , Peptide Hydrolases/metabolism , Activating Transcription Factor 1/metabolism , Adenylyl Cyclases/metabolism , Amino Acid Sequence , Animal Feed/adverse effects , Animals , Calpain/metabolism , Cathepsins/metabolism , Clenbuterol/pharmacology , Cyclic AMP/metabolism , DNA, Complementary , Molecular Sequence Data , Muscles/enzymology , Phenethylamines/pharmacology , Proteasome Endopeptidase Complex/metabolism , Receptors, Adrenergic, beta-2/metabolism , Sequence Homology, Amino AcidABSTRACT
OBJECTIVE: Chronic mechanical unloading induces left ventricular (LV) atrophy, which may impair functional recovery during support with an LV-assist device. Clenbuterol, a beta2-adrenergic receptor (AR) agonist, is known to induce myocardial hypertrophy and might prevent LV atrophy during LV unloading. Furthermore, beta2-AR stimulation is reported to improve Ca2+ handling and contribute to antiapoptosis. However, there is little information on the effects of clenbuterol during LV unloading. METHODS AND RESULTS: We investigated LV atrophy and function after LV unloading produced by heterotopic heart transplantation in isogenic rats. After transplantation, rats were randomized to 1 of 2 groups (n=10 each). The clenbuterol group received 2 mg.kg(-1).d(-1) of the drug for 2 weeks; the control group received normal saline. The weight of unloaded control hearts was 48% less than that of host hearts after 2 weeks of unloading. Clenbuterol significantly increased the weight of the host hearts but did not prevent unloading-induced LV atrophy. Papillary muscles were isolated and stimulated, and there was no difference in developed tension between the 2 groups. However, the inotropic response to the beta-AR agonist isoproterenol significantly improved in the clenbuterol group. The mRNA expression of myocardial sarco(endo)plasmic reticulum Ca2+-ATPase 2a (SERCA2a) and fetal gene shift (myosin heavy chain [MHC] mRNA isozyme) was also significantly improved by clenbuterol treatment. There was no difference in beta1-AR mRNA expression between the 2 groups. In contrast, beta2-AR mRNA was significantly decreased in the clenbuterol-treated, unloaded heart. This indicates that clenbuterol may downregulate beta2-ARs. In the evaluation of apoptosis, mRNA expression of caspase-3, which is the central pathway for apoptosis, tended to be better in the clenbuterol group. CONCLUSIONS: During complete LV unloading, clenbuterol did not prevent myocardial atrophy but improved gene expression (SERCA2a, beta-MHC) and beta-adrenergic responsiveness and potentially prevented myocardial apoptosis. However, chronic administration of clenbuterol may be associated with downregulation of beta2-ARs.
Subject(s)
Adrenergic beta-Agonists/therapeutic use , Clenbuterol/therapeutic use , Heart/drug effects , Adrenergic beta-Agonists/pharmacology , Animals , Atrophy , Calcium-Transporting ATPases/biosynthesis , Calcium-Transporting ATPases/genetics , Caspase 3 , Caspases/biosynthesis , Caspases/genetics , Clenbuterol/pharmacology , Down-Regulation/drug effects , Drug Evaluation, Preclinical , Enzyme Induction/drug effects , Gene Expression Regulation/drug effects , Heart Transplantation , Heart Ventricles/drug effects , Heart Ventricles/pathology , Heart Ventricles/physiopathology , Isoproterenol/pharmacology , Male , Myocardial Contraction/drug effects , Myocardium/pathology , Myosin Heavy Chains/biosynthesis , Myosin Heavy Chains/genetics , Organ Size , Papillary Muscles/drug effects , Papillary Muscles/physiopathology , Protein Isoforms/biosynthesis , Protein Isoforms/genetics , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Random Allocation , Rats , Rats, Inbred Lew , Receptors, Adrenergic, beta-1/biosynthesis , Receptors, Adrenergic, beta-1/genetics , Receptors, Adrenergic, beta-2/biosynthesis , Receptors, Adrenergic, beta-2/drug effects , Receptors, Adrenergic, beta-2/genetics , Sarcoplasmic Reticulum Calcium-Transporting ATPases , Stress, Mechanical , Transplantation, Heterotopic , Transplantation, Isogeneic , Ventricular Function, Left/drug effectsABSTRACT
Illegal dietary supplementation with beta(2)-agonists has been shown to increase protein deposition and decrease fat accretion in domestic animals. In poultry the metabolic and endocrine responses to beta(2)-agonists are not fully elucidated. In this trial the effects of dietary clenbuterol (1 p.p.m.) and cimaterol (1 p.p.m.) on muscle composition and endocrine response of male broiler chickens were studied. Dietary clenbuterol induced a slight, but in general not significant, improvement of zootechnical performances and carcass yields. Chemical composition of muscle was not influenced by dietary treatments, even if a slight improvement of protein content was observed in treated groups. No effects on fatty acid composition of meat were detected. Both clenbuterol and cimaterol treatments caused a downregulation in testicular androgen receptors and in pulmonary, cardiac and central nervous system beta-adrenergic receptors.
Subject(s)
Adrenergic beta-Agonists/administration & dosage , Body Composition/drug effects , Chickens/metabolism , Clenbuterol/administration & dosage , Ethanolamines/administration & dosage , Muscle, Skeletal/drug effects , Receptors, Androgen/drug effects , Adrenergic beta-Agonists/pharmacology , Animal Feed , Animals , Chickens/anatomy & histology , Chickens/growth & development , Clenbuterol/pharmacology , Dietary Supplements , Down-Regulation/drug effects , Ethanolamines/pharmacology , Male , Muscle, Skeletal/metabolism , Random Allocation , Receptors, Adrenergic, beta/drug effects , Receptors, Adrenergic, beta/metabolism , Receptors, Androgen/metabolism , Weight GainABSTRACT
PURPOSE: This study was aimed at investigating the role of betaadrenoceptor subtypes in mediating the relaxation and contraction of seminal vesicles in rabbits. MATERIALS AND METHODS: Relaxation or contractile responses of epithelium- removed muscle strips of a rabbit seminal vesicle, which were precontracted with 10-5M norepinephrine, to selective betasubtypes-adrenoceptor agonists were observed in an organ bath. The contractile responses induced by isoproterenol were also observed after application of selective antagonists. RESULTS: Isoproterenol showed a concentration-dependent contractile response, but the contractility was weaker than those with phenylephrine and norepinephrine. The betaselective-agonists(xamoterol for beta, clenbuterol for beta and BRL37344 for beta) alone evoked neither contraction nor relaxation. However, the beta- and beta-agonists inhibited the contraction of the precontracted strips with 10-5M norepinephrine, while the beta-agonist enhanced the contraction. The pretreatment with a beta-antagonist(ICI118551) reduced the tension of the strips developed by 10-4M isoproterenol, but the beta-(atenolol) and beta-(SR59230A) antagonists showed no changes in the response. CONCLUSIONS: beta- and beta-adrenoceptors seem to mediate the relaxation of the seminal vesicle, while the beta-adrenoceptor may have a supplementary role in contraction.
Subject(s)
Rabbits , Baths , Clenbuterol , Isoproterenol , Negotiating , Norepinephrine , Phenylephrine , Relaxation , Seminal VesiclesABSTRACT
BACKGROUND: Muscle wasting and dysfunction is a significant problem in prolonged exposure to microgravity. HYPOTHESIS: This study tested the hypothesis that a beta-adrenergic agonist (clenbuterol) could attenuate the effects of 14 d of unweighting on mixed fiber type skeletal muscle. METHODS: Female, Sprague-Dawley rats were maintained in cages as: 1. controls (C; n = 12); 2. hindlimb suspended via tail casting (HLU; n = 12); 3. clenbuterol injected daily (3 mg x kg(-1)) (CL; n = 10); or 4. hindlimb suspended and injected with clenbuterol daily (3 mg x kg(-1)) (HLU + CL; n = 12). RESULTS: At the end of the study, both CL and HLU + CL had higher body weights compared with HLU (p < 0.05). Gastrocnemius mass (wet weight and muscle weight/body weight) and maximal tetanic force were significantly decreased during HLU (p < 0.05) (mean +/- SE; mass: C = 1.6 +/- 0.04 g, HLU = 1.2 +/- 0.05 g force: C = 3483 +/- 113 g, HLU = 2765 +/- 52 g). Clenbuterol attenuated the decrease in both mass and force generation (mass: HLU + CL = 1.4 +/- 0.04 g; force: HLU + CL = 3162 +/- 135). Twitch tension during HLU (1057 +/- 72 g) was significantly less (p < 0.05) than during C (1362 +/- 61 g), and clenbuterol did not attenuate this loss. HLU caused a decrease (p < 0.05) in force at 30 Hz and decreased one-half relaxation time (1/2 RT) (p < 0.05) from 30 +/- 2 to 25 +/- 2 ms. Clenbuterol caused further decreases (p < 0.05) in both force (20 and 30 Hz) and 1/2 RT. CONCLUSIONS: These data suggest that a beta-adrenergic agonist may be of benefit in attenuating wasting and the reduced maximal force seen during periods of unweighting in mixed fiber type muscle.
Subject(s)
Adrenergic beta-Agonists/therapeutic use , Clenbuterol/therapeutic use , Disease Models, Animal , Hindlimb Suspension/adverse effects , Muscular Atrophy/etiology , Muscular Atrophy/prevention & control , Adrenergic beta-Agonists/pharmacology , Animals , Body Weight/drug effects , Body Weight/physiology , Calcium-Transporting ATPases/drug effects , Calcium-Transporting ATPases/physiology , Clenbuterol/pharmacology , Drug Evaluation, Preclinical , Female , Injections, Intramuscular , Muscle Contraction/drug effects , Muscle Contraction/physiology , Muscle, Skeletal/drug effects , Muscle, Skeletal/physiology , Muscular Atrophy/pathology , Muscular Atrophy/physiopathology , Organ Size/drug effects , Organ Size/physiology , Rats , Rats, Sprague-Dawley , Sarcoplasmic Reticulum Calcium-Transporting ATPasesABSTRACT
Antecedentes: El propósito del estudio fue conocer los hábitos alimentarlos, de consumo de ayudas ergogénicas y de actividad fisica en culturistas. Adicionalmente, valorar su composición corporal y sus niveles de metabolitos en plasma sanguíneo. Material y métodos.- Se diseñó un estudio transversal, descriptivo y analítico, en el que participaron 16 culturistas varones de nivel nacional que entrenaban en la fase de volumen, tres meses antes de la competición. Se aplicaron: un cuestionario de frecuencia de consumo de alimentos, un registro de ingestas de 14 días, una entrevista semi-estructurada para conocer el consumo de ayudas ergogénicas y las características del entrenamiento, un estudio antropométrico y una analítica plasmática de rutina. El análisis de datos se hizo mediante la prueba t-student y regresión lineal simple. Resultados: Los culturistas consumían dos o más anabolizantes androgénicos, uno de los cuales era testosterona y, además, clenbuterol recibiendo dos o más dosis semanales de anabolizante. El consumo medio diario de energía fue de 3.200 K-calorías y de proteínas, 2,5 g/kg. Los sujetos con ingesta proteica superior a 3,0 glkgídía (media 3,6 g/kg/día) presentaron mayor aporte de otros nutrientes (hierro y vitaminas B, B6y B,,) (P<0,05) y niveles plasmáticos elevados de urea (AU)
Subject(s)
Adult , Male , Humans , Exercise/physiology , Sports , Feeding Behavior , Muscle Development , Food, Fortified , Clenbuterol/administration & dosage , Body Composition , Nutritional Status , Anabolic Agents/administration & dosageABSTRACT
The effects of lipoic acid (LA) on muscle growth, metabolic response and hepatic respiration in broilers treated with or without clenbuterol (CLE) were examined. In 4-week-old chickens, dietary LA administration (100 mg x kg(-1)) enhanced the beta-adrenergic response of plasma nonesterified fatty acid with an intravenous injection of CLE (50 microg x kg(-1), estimated from the response area for 120 min (-7,860 vs. 874 micromol x L(-1) min in control and LA-treated groups, respectively; P < 0.05). When chickens received long-term oral administration of CLE (0.25 mg x kg(-1)) for 30 d, LA interfered with the repartitioning action of CLE, decreased abdominal fat weight (P < 0.05) and increased protein concentration of the breast muscle (P < 0.05), in 7-week-old chickens. In addition, the LA supplementation alone increased both plasma nonesterified fatty acid (P < 0.05) and triacylglycerol (P < 0.05), whereas these effects were not associated with CLE administration. These findings suggest that the dietary LA level used stimulates rapid lipolytic response of plasma nonesterified fatty acid to CLE injection and fatty acid turnover between adipose tissue and the liver, but does not facilitate the repartitioning action of CLE during long-term treatment in broilers.
Subject(s)
Adrenergic beta-Agonists/pharmacology , Antioxidants/pharmacology , Chickens/metabolism , Clenbuterol/pharmacology , Lipid Metabolism , Thioctic Acid/pharmacology , Adipose Tissue/drug effects , Adipose Tissue/growth & development , Adipose Tissue/metabolism , Administration, Oral , Adrenergic beta-Agonists/administration & dosage , Animals , Antioxidants/administration & dosage , Antioxidants/metabolism , Blood Glucose/metabolism , Body Weight/drug effects , Chickens/growth & development , Clenbuterol/administration & dosage , Fatty Acids, Nonesterified/blood , Female , Injections, Intravenous/veterinary , Lipolysis , Liver/drug effects , Liver/metabolism , Muscle, Skeletal/drug effects , Muscle, Skeletal/growth & development , Muscle, Skeletal/metabolism , Oxygen Consumption/drug effects , Thioctic Acid/administration & dosage , Thioctic Acid/metabolism , Triglycerides/metabolismABSTRACT
1. We examined the effects of thiamine-hydrochloride (10 mg/kg body weight) and a beta-agonist, clenbuterol (50 microg/kg body weight), on plasma metabolites and hepatic oxygen consumption in female broiler chicks. 2. Clenbuterol, thiamine or both, dissolved in saline, were injected into thigh muscle on 2, 4 and 6 d of age. At 7 d of age blood samples in each treatment group were obtained and breast muscle and liver were weighed; liver slices were used for measurement of oxygen consumption. 3. Body weight gain was reduced by clenbuterol. Thiamine increased breast muscle weight as a proportion of body weight regardless of clenbuterol dose. Clenbuterol increased relative liver weight markedly, especially when chicks received thiamine also. 4. Clenbuterol increased plasma free fatty acid concentration in chicks treated with thiamine. Thiamine decreased plasma triglyceride regardless of clenbuterol dose. Plasma glucose concentration was decreased by both thiamine and clenbuterol. 5. The absolute rate of oxygen consumption in liver slices was greater in the thiamine-treated chicks; clenbuterol did not affect hepatic oxygen consumption. 6. These findings suggest that thiamine-induced energy expenditure results not only from thermogenesis in the liver, but also from increasing energy utilisation for muscle hypertrophy and this vitamin supplementation facilitates the lipolytic effects of the beta-agonist.