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Current Opinion in Pharmacology Oct 2021Skeletal muscle atrophy is a hallmark of severe spinal cord injury (SCI) that is precipitated by the neural insult and paralysis. Additionally, other factors may... (Review)
Review
Skeletal muscle atrophy is a hallmark of severe spinal cord injury (SCI) that is precipitated by the neural insult and paralysis. Additionally, other factors may influence muscle loss, including systemic inflammation, low testosterone, low insulin-like growth factor (IGF)-1, and high-dose glucocorticoid treatment. The signaling cascades that drive SCI-induced muscle loss are common among most forms of disuse atrophy and include ubiquitin-proteasome signaling and others. However, differing magnitudes and patterns of atrophic signals exist after SCI versus other disuse conditions and are accompanied by endogenous inhibition of IGF-1/PI3K/Akt signaling, which combine to produce exceedingly rapid atrophy. Several well-established anabolic agents, including androgens and myostatin inhibitors, display diminished ability to prevent SCI-induced atrophy, while ursolic acid and β2-agonists more effectively attenuate muscle loss. Strategies combining physical rehabilitation regimens to reload the paralyzed limbs with drugs targeting the underlying molecular pathways hold the greatest potential to improve muscle recovery after severe SCI.
Topics: Humans; Muscle, Skeletal; Muscular Atrophy; Pharmaceutical Preparations; Spinal Cord Injuries
PubMed: 34461564
DOI: 10.1016/j.coph.2021.07.023 -
RSC Advances Nov 2022A novel label-free aptasensor for the specific detection of clenbuterol was developed through the fluorescence resonance energy transfer (FRET) mechanism by using an...
A novel label-free aptasensor for the specific detection of clenbuterol was developed through the fluorescence resonance energy transfer (FRET) mechanism by using an aptamer as the target recognition element, rhodamine B (RhoB) as the fluorescence probe and graphene oxide (GO) as the fluorescence quencher. In the absence of clenbuterol, the aptamer was adsorbed on the surface of GO, preventing the interaction between RhoB and GO, and a high fluorescence signal was obtained. In the presence of clenbuterol, the aptamer specially bound to clenbuterol with a high affinity and detached from the surface of GO, while positively charged rhodamine B could be electrostatically adsorbed onto the surface of GO, thus quenching the fluorescence. By comparing the fluorescence intensity before and after the addition of clenbuterol, a simple and fast fluorescence assay for clenbuterol was established with a detection range of 100-700 nM and a detection limit of 9.6 nM. Moreover, the proposed method was successfully applied in the determination of clenbuterol in pork samples with recoveries in the range of 96.75-104.91% and a relative standard deviation of less than 5.67%. Because of its easy operation, fast response, low cost and competitive analytical performance, this method is a promising candidate for the detection of clenbuterol and can be extended to the detection of other targets by changing the corresponding aptamers.
PubMed: 36425698
DOI: 10.1039/d2ra06260g -
European Journal of Case Reports in... 2020We present a case of a 22-year-old bodybuilder diagnosed with myocarditis secondary to clenbuterol use.
OBJECTIVE
We present a case of a 22-year-old bodybuilder diagnosed with myocarditis secondary to clenbuterol use.
RESULTS
The patient was primarily managed conservatively by the discontinuation of clenbuterol and the temporary use of dual anti-platelets, beta-blockers and nitrates.
CONCLUSION
Clenbuterol is a long-acting beta-2 agonist primarily used in veterinary medicine. In recent years, it has been illegally marketed as a weight loss supplement because of its anabolic properties and is popular among fitness enthusiasts. It is our aim to use this case to underscore the adverse effects of this drug with hopes that tighter regulations will be instituted to stem its illegal distribution.
LEARNING POINTS
Clenbuterol is primarily a veterinary drug with bronchodilator and tocolytic properties.It is illegally used as a performance enhancer by athletes and bodybuilders because of its anabolic properties.Clenbuterol misuse can result in myocardial injury.
PubMed: 32908823
DOI: 10.12890/2020_001662 -
Brain, Behavior, and Immunity Nov 2022While inflammation has been implicated in psychopathology, relationships between immune-suppressing processes and psychiatric constructs remain elusive. This study...
While inflammation has been implicated in psychopathology, relationships between immune-suppressing processes and psychiatric constructs remain elusive. This study sought to assess whether β-agonist clenbuterol (CBL) would attenuate immune activation in adolescents with mood and anxiety symptoms following ex vivo exposure of whole blood to lipopolysaccharide (LPS). Our focus on adolescents aimed to target a critical developmental period when psychiatric conditions often emerge and prior to chronicity effects. To capture a diverse range of immunologic and symptomatologic phenotypes, we included 97 psychotropic-medication free adolescents with mood and anxiety symptoms and 33 healthy controls. All participants had comprehensive evaluations and dimensional assessments of psychiatric symptoms. Fasting whole-blood samples were collected and stimulated with LPS in the presence and absence of CBL for 6 hours, then analyzed for 41 cytokines, chemokines, and hematopoietic growth factors. Comparison analyses used Bonferroni-corrected nonparametric tests. Levels of nine immune biomarkers-including IL-1RA, IL-1β, IL-6, IP-10, MCP-1, MIP-1α, MIP-1β, TGF-α, and TNF-α-were significantly reduced by CBL treatment compared to LPS alone. Exploratory factor analysis reduced 41 analytes into 5 immune factors in each experimental condition, and their relationships with psychiatric symptoms were examined as a secondary aim. CBL + LPS Factor 4-comprising EGF, PDGF-AA, PDGF-AB/BB, sCD40L, and GRO-significantly correlated with anticipatory and consummatory anhedonia, even after controlling for depression severity. This study supports the possible inhibitory effect of CBL on immune activation. Using a data-driven method, distinctive relationships between CBL-affected immune biomarkers and dimensional anhedonia were reported, further elucidating the role of β-agonism in adolescent affective symptomatology.
Topics: Anhedonia; Biomarkers; Chemokine CCL3; Chemokine CCL4; Chemokine CXCL10; Clenbuterol; Cytokines; Epidermal Growth Factor; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-6; Lipopolysaccharides; Transforming Growth Factor alpha; Tumor Necrosis Factor-alpha
PubMed: 35914697
DOI: 10.1016/j.bbi.2022.07.163 -
Biosensors Oct 2022Clenbuterol (CB) is a synthetic -receptor agonist which can be used to improve carcass leanness in swine, but its residues in pork also pose health risks. In this...
Clenbuterol (CB) is a synthetic -receptor agonist which can be used to improve carcass leanness in swine, but its residues in pork also pose health risks. In this report, surface-enhanced Raman scattering (SERS) technology was used to achieve rapid detection and identification of clenbuterol hydrochloride (CB) residues. First, the effects of several different organic solvents on the extraction efficiency were compared, and it was found that clenbuterol in pork had a better enhancement effect using ethyl acetate as an extraction agent. Then, SERS signals of clenbuterol in different solvents were compared, and it was found that clenbuterol had a better enhancement effect in an aqueous solution. Therefore, water was chosen as the solvent for clenbuterol detection. Next, enhancement effect was compared using different concentration of sodium chloride solution as the aggregating compound. Finally, pork samples with different clenbuterol content (1, 3, 5, 7, 9, and 10 µg/g) were prepared for quantitative analysis. The SERS spectra of samples were collected with 0.5 mol/L of NaCl solution as aggregating compound and gold colloid as an enhanced substrate. Multiple scattering correction (MSC) and automatic Whittaker filter (AWF) were used for preprocessing, and the fluorescence background contained in the original Raman spectra was removed. A unary linear regression model was established between SERS intensity at 1472 cm and clenbuterol content in pork samples. The model had a better linear relationship with a correlation coefficient of 0.99 and a root mean square error of 0.263 µg/g. This method can be used for rapid screening of pork containing clenbuterol in the market.
Topics: Swine; Animals; Clenbuterol; Spectrum Analysis, Raman; Sodium Chloride; Pork Meat; Gold; Red Meat; Gold Colloid; Water; Solvents
PubMed: 36290996
DOI: 10.3390/bios12100859 -
Se Pu = Chinese Journal of... Dec 2021Clenbuterol enantiomers differ greatly in their bioactivities. By optimizing the conditions for chromatographic separation and method validation, ultra-performance...
Clenbuterol enantiomers differ greatly in their bioactivities. By optimizing the conditions for chromatographic separation and method validation, ultra-performance convergence chromatography (UPC) was adopted to separate the enantiomers of clenbuterol. Standard solutions of (+)-clenbuterol and (-)-clenbuterol were stored at -18 ℃ for 1, 3, 5, 7, 14, 30, and 60 d, and then, their stability was monitored. The impacts of different chromatographic columns, cosolvents, system backpressure, and chromatographic column temperature on the separation of the two enantiomers were investigated. Acquity Trefoil AMY1 (150 mm×3.0 mm, 2.5 μm) was used for separation, and CO-0.5% (v/v) ammonium acetate was used as the mobile phase. Gradient elution at a flow rate of 2.0 mL/min was adopted. The detection wavelength was set to 241 nm, and the injection volume was set to 10 μL. The backpressure was set to 13.8 MPa, and the column temperature was maintained at 40 ℃. The two enantiomers showed good linear relationships in the range of 1.0 to 20.0 mg/L with correlation coefficients greater than 0.9997. The limits of detection (LODs, =3) of (+)-clenbuterol and (-)-clenbuterol were both 0.5 mg/L. The relative standard deviation (RSD, =6) for the peak area of the 10.0 mg/L mixed standard working solution with six replicate injections ranged from 0.65% to 0.76%. The effectiveness and practicability of this method were demonstrated by using it to detect standard clenbuterol racemate. The (+)-clenbuterol and (-)-clenbuterol contents were 5.6 mg/L and 5.5 mg/L, respectively, in the standard clenbuterol racemates, as determined by the external standard method of quantification. The detection results suggested that the content ratio of (+)-clenbuterol and (-)-clenbuterol was close to 1.02∶1.00, which is consistent with the literature data. The established method has the advantages of rapid analysis, good separation effect, and low consumption of organic solvents, and it is suitable for the separation of clenbuterol enantiomers. This method can also provide technical support for the separation of other chiral drugs, analysis of the effects of chiral drugs, and assessment of product quality.
Topics: Chromatography, High Pressure Liquid; Clenbuterol; Solvents; Stereoisomerism
PubMed: 34812007
DOI: 10.3724/SP.J.1123.2021.06045 -
Pharmacology & Therapeutics Apr 2019Cancer cachexia is a multifactorial syndrome that develops during malignant tumor growth. Changes in plasma levels of several hormones and inflammatory factors result in... (Review)
Review
Cancer cachexia is a multifactorial syndrome that develops during malignant tumor growth. Changes in plasma levels of several hormones and inflammatory factors result in an intense catabolic state, decreased activity of anabolic pathways, anorexia, and marked weight loss, leading to cachexia development and/or accentuation. Inflammatory mediators appear to be related to the control of a highly regulated process of muscle protein degradation that accelerates the process of cachexia. Several mediators have been postulated to participate in this process, including TNF-α, myostatin, and activated protein degradation pathways. Some interventional therapies have been proposed, including nutritional (dietary, omega-3 fatty acid supplementation), hormonal (insulin), pharmacological (clenbuterol), and nonpharmacological (physical exercise) therapies. Omega-3 (n-3) polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid, are recognized for their anti-inflammatory properties and have been used in therapeutic approaches to treat or attenuate cancer cachexia. In this review, we discuss recent findings on cellular and molecular mechanisms involved in inflammation in the cancer cachexia syndrome and the effectiveness of n-3 PUFAs to attenuate or prevent cancer cachexia.
Topics: Animals; Cachexia; Fatty Acids, Omega-3; Humans; Neoplasms
PubMed: 30521881
DOI: 10.1016/j.pharmthera.2018.12.001 -
American Journal of Physiology.... Mar 2021Prolonged supplementation with the β-agonist clenbuterol improves glucose homeostasis in diabetic rodents, likely via β-adrenoceptor (β-AR)-mediated effects in the...
Prolonged supplementation with the β-agonist clenbuterol improves glucose homeostasis in diabetic rodents, likely via β-adrenoceptor (β-AR)-mediated effects in the skeletal muscle and liver. However, since rodents have, in contrast to-especially diabetic-humans, substantial quantities of brown adipose tissue (BAT) and clenbuterol has affinity to β- and β-ARs, the contribution of BAT to these improvements is unclear. Therefore, we investigated clenbuterol-mediated improvements in glucose homeostasis in uncoupling protein 1-deficient () mice, lacking thermogenic BAT, versus wild-type (WT) mice. Anesthetized WT and C57Bl/6 mice were injected with saline or clenbuterol and whole body oxygen consumption was measured. Furthermore, male WT and C57Bl/6 mice were subjected to 17-wk of chow feeding, high-fat feeding, or high-fat feeding with clenbuterol treatment between and . Body composition was measured weekly with MRI. Oral glucose tolerance and insulin tolerance tests were performed in and , respectively. Clenbuterol increased oxygen consumption approximately twofold in WT mice. This increase was blunted in mice, indicating clenbuterol-mediated activation of BAT thermogenesis. High-fat feeding induced diabetogenic phenotypes in both genotypes. However, low-dose clenbuterol treatment for 2 wk significantly reduced fasting blood glucose by 12.9% in WT and 14.8% in mice. Clenbuterol treatment improved glucose and insulin tolerance in both genotypes compared with HFD controls and normalized to chow-fed control mice independent of body mass and composition alterations. Clenbuterol improved whole body glucose homeostasis independent of UCP1. Given the low human abundancy of BAT, β-AR agonist treatment provides a potential novel route for glucose disposal in diabetic humans. Improvements in whole body glucose homeostasis of rodents upon prolonged β-adrenergic agonist supplementation could potentially be attributed to UCP1-mediated BAT thermogenesis. Indeed, we show that acute injection with the β-AR agonist clenbuterol induces BAT activation in mice. However, we also demonstrate that prolonged clenbuterol supplementation robustly improves whole body glucose and insulin tolerance in a similar way in both DIO WT and mice, indicating that β-AR agonist supplementation improves whole body glucose homeostasis independent of UCP1-mediated BAT thermogenesis.
Topics: Adipose Tissue, Brown; Adrenergic beta-2 Receptor Agonists; Animals; Clenbuterol; Diet, High-Fat; Drug Administration Schedule; Glucose; Glucose Intolerance; Homeostasis; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Obesity; Receptors, Adrenergic, beta-2; Thermogenesis; Time Factors; Uncoupling Protein 1
PubMed: 33522400
DOI: 10.1152/ajpendo.00324.2020 -
Journal of Physiology and Pharmacology... Mar 2008The present study was designed to determine the involvement of nitric oxide (NO) and prostaglandins (PG) in the stimulatory action of clenbuterol, a selective...
The present study was designed to determine the involvement of nitric oxide (NO) and prostaglandins (PG) in the stimulatory action of clenbuterol, a selective beta(2)-adrenergic receptor agonist on hypothalamic-pituitary-adrenal (HPA) axis under basal and social crowding stress conditions. Clenbuterol given i.c.v. (10 microg) or i.p. (0.2 mg/kg) considerably increased ACTH and corticosterone secretion. A selective beta(2)-receptor antagonist compound ICI 118551 and non-selective beta-receptor antagonist propranolol given by either route reduced the stimulatory action of clenbuterol. Crowding stress (21 rats in a cage for 7) for 3-7 days significantly reduced the i.c.v. clenbuterol-induced ACTH and corticosterone secretion and i.p. clenbuterol-elicited ACTH secretion. L-NAME, mainly endothelial nitric oxide synthase (NOS) blocker, stronger than L-NNA, a neuronal NOS blocker, reduced the clenbuterol-evoked ACTH and corticosterone secretion in control rats but did not significantly alter this secretion already reduced by crowding stress. Piroxicam, predominantly constitutive cyclooxygenase (COX-1) inhibitor, given i.p. significantly diminished the i.p. clenbuterol-induced ACTH and corticosterone secretion in control rats and tended to reverse the reduction of ACTH secretion by crowding stress. These results indicate that clenbuterol, a selective beta(2)-adrenoceptor agonist, is much stronger stimulator of the HPA axis than isoprenaline, a non-selective beta-receptor agonist. Social crowding stress reduces to a larger extent the HPA response to beta(2)-receptor stimulation. Likewise, in the HPA axis stimulation via beta(2)-adrenoceptors endogenous NO and prostaglandins are significantly involved. Beta2-adrenoceptor is a dominant functional subtype of beta-receptor in the stimulatory and modulatory signals regulating the HPA axis activity under basal and social stress conditions.
Topics: Adrenergic beta-Agonists; Adrenocorticotropic Hormone; Animals; Clenbuterol; Corticosterone; Crowding; Hypothalamo-Hypophyseal System; Injections, Intraperitoneal; Injections, Intraventricular; Male; Nitric Oxide; Pituitary-Adrenal System; Prostaglandins; Rats; Rats, Wistar; Receptors, Adrenergic, beta-2; Stress, Psychological
PubMed: 18441396
DOI: No ID Found -
Substance Abuse Treatment, Prevention,... Mar 2015As far as we are aware, no previous systematic review and synthesis of the qualitative/descriptive literature on polypharmacy in anabolic-androgenic steroid(s) (AAS)... (Review)
Review
BACKGROUND
As far as we are aware, no previous systematic review and synthesis of the qualitative/descriptive literature on polypharmacy in anabolic-androgenic steroid(s) (AAS) users has been published.
METHOD
We systematically reviewed and synthesized qualitative/descriptive literature gathered from searches in electronic databases and by inspecting reference lists of relevant literature to investigate AAS users' polypharmacy. We adhered to the recommendations of the UK Economic and Social Research Council's qualitative research synthesis manual and the PRISMA guidelines.
RESULTS
A total of 50 studies published between 1985 and 2014 were included in the analysis. Studies originated from 10 countries although most originated from United States (n=22), followed by Sweden (n=7), England only (n=5), and the United Kingdom (n=4). It was evident that prior to their debut, AAS users often used other licit and illicit substances. The main ancillary/supplementary substances used were alcohol, and cannabis/cannabinoids followed by cocaine, growth hormone, and human chorionic gonadotropin (hCG), amphetamine/meth, clenbuterol, ephedra/ephedrine, insulin, and thyroxine. Other popular substance classes were analgesics/opioids, dietary/nutritional supplements, and diuretics. Our classification of the various substances used by AAS users resulted in 13 main groups. These non-AAS substances were used mainly to enhance the effects of AAS, combat the side effects of AAS, and for recreational or relaxation purposes, as well as sexual enhancement.
CONCLUSIONS
Our findings corroborate previous suggestions of associations between AAS use and the use of other licit and illicit substances. Efforts must be intensified to combat the debilitating effects of AAS-associated polypharmacy.
Topics: Anabolic Agents; Androgens; Drug Users; Humans; Polypharmacy; Self Medication
PubMed: 25888931
DOI: 10.1186/s13011-015-0006-5