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International Journal of Molecular... Jul 2015In the present study, we aimed to determine whether ethanol extracts of Fructus Schisandrae (FS), the dried fruit of Schizandra chinensis Baillon, mitigates the...
In the present study, we aimed to determine whether ethanol extracts of Fructus Schisandrae (FS), the dried fruit of Schizandra chinensis Baillon, mitigates the development of dexamethasone-induced muscle atrophy. Adult SPF/VAT outbred CrljOri:CD1 (ICR) mice were either treated with dexamethasone to induce muscle atrophy. Some mice were treated with various concentrations of FS or oxymetholone, a 17α-alkylated anabolic-androgenic steroid. Muscle thickness and weight, calf muscle strength, and serum creatine and creatine kinase (CK) levels were then measured. The administration of FS attenuated the decrease in calf thickness, gastrocnemius muscle thickness, muscle strength and weight, fiber diameter and serum lactate dehydrogenase levels in the gastrocnemius muscle bundles which was induced by dexamethasone in a dose-dependent manner. Treatment with FS also prevented the dexamethasone-induced increase in serum creatine and creatine kinase levels, histopathological muscle fiber microvacuolation and fibrosis, and the immunoreactivity of muscle fibers for nitrotyrosine, 4-hydroxynonenal, inducible nitric oxide synthase and myostatin. In addition, the destruction of the gastrocnemius antioxidant defense system was also inhibited by the administration of FS in a dose-dependent manner. FS downregulated the mRNA expression of atrogin-1 and muscle ring-finger protein-1 (involved in muscle protein degradation), myostatin (a potent negative regulator of muscle growth) and sirtuin 1 (a representative inhibitor of muscle regeneration), but upregulated the mRNA expression of phosphatidylinositol 3-kinase, Akt1, adenosine A1 receptor and transient receptor potential cation channel subfamily V member 4, involved in muscle growth and the activation of protein synthesis. The overall effects of treatment with 500 mg/kg FS were comparable to those observed following treatment with 50 mg/kg oxymetholone. The results from the present study support the hypothesis that FS has a favorable ameliorating effect on muscle atrophy induced by dexamethasone, by exerting anti-inflammatory and antioxidant effects on muscle fibers, which may be due to an increase in protein synthesis and a decrease in protein degradation.
Topics: Aldehydes; Animals; Anti-Inflammatory Agents; Antioxidants; Creatine; Creatine Kinase; Dexamethasone; Drugs, Chinese Herbal; Fibrosis; L-Lactate Dehydrogenase; Mice; Mice, Inbred ICR; Muscle Proteins; Muscle Strength; Muscle Tonus; Muscle, Skeletal; Muscular Atrophy; Myostatin; Nitric Oxide Synthase Type II; Oxymetholone; Phosphatidylinositol 3-Kinase; Protein Biosynthesis; Proto-Oncogene Proteins c-akt; RNA, Messenger; Receptor, Adenosine A1; SKP Cullin F-Box Protein Ligases; Schisandra; Sirtuin 1; TRPV Cation Channels; Tripartite Motif Proteins; Tyrosine; Ubiquitin-Protein Ligases
PubMed: 25955031
DOI: 10.3892/ijmm.2015.2200 -
Stem Cell Reports Jan 2015Androgens are widely used for treating Fanconi anemia (FA) and other human bone marrow failure syndromes, but their mode of action remains incompletely understood. Aged...
Androgens are widely used for treating Fanconi anemia (FA) and other human bone marrow failure syndromes, but their mode of action remains incompletely understood. Aged Fancd2(-/-) mice were used to assess the therapeutic efficacy of oxymetholone (OXM) and its mechanism of action. Eighteen-month-old Fancd2(-/-) mice recapitulated key human FA phenotypes, including reduced bone marrow cellularity, red cell macrocytosis, and peripheral pancytopenia. As in humans, chronic OXM treatment significantly improved these hematological parameters and stimulated the proliferation of hematopoietic stem and progenitor cells. RNA-Seq analysis implicated downregulation of osteopontin as an important potential mechanism for the drug's action. Consistent with the increased stem cell proliferation, competitive repopulation assays demonstrated that chronic OXM therapy eventually resulted in stem cell exhaustion. These results expand our knowledge of the regulation of hematopoietic stem cell proliferation and have direct clinical implications for the treatment of bone marrow failure.
Topics: Animals; Blood Cell Count; Bone Marrow; Cell Cycle; Cell Proliferation; Disease Models, Animal; Fanconi Anemia; Fanconi Anemia Complementation Group D2 Protein; Gene Expression Regulation; Hematopoiesis; Hematopoietic Stem Cells; Humans; Mice; Mice, Knockout; Osteopontin; Oxymetholone; Pancytopenia; Sequence Analysis, RNA; Time Factors; Transcription, Genetic
PubMed: 25434823
DOI: 10.1016/j.stemcr.2014.10.014 -
The Cochrane Database of Systematic... Oct 2014Anaemia occurs when blood contains fewer red blood cells and lower haemoglobin levels than normal, and is a common complication among adults with chronic kidney disease... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Anaemia occurs when blood contains fewer red blood cells and lower haemoglobin levels than normal, and is a common complication among adults with chronic kidney disease (CKD). Although a number of approaches are applied to correct anaemia in adults with CKD, the use of androgen therapy is controversial.
OBJECTIVES
The aim of this review was to determine the benefits and harms of androgens for the treatment of anaemia in adult patients with CKD.
SEARCH METHODS
We searched CENTRAL, the Cochrane Renal Group's Specialised Register, the Chinese Biomedicine Database (CBM), CNKI, VIP and reference lists of articles without language restriction. The most recent search was conducted in August 2014.
SELECTION CRITERIA
All randomised controlled trials (RCTs) that assessed the use of androgens for treating anaemia of CKD in adults were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed risk of bias in the included studies. Meta-analyses were performed using relative risk (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI).
MAIN RESULTS
We included eight studies that reported data from 181 participants. Study quality was assessed as moderate in six studies, one was low quality, and one was high quality. The small number of included studies, and low participant numbers adversely influenced evidence quality overall.We found limited evidence (1 study, 24 participants) to indicate that oxymetholone can increase haemoglobin (Hb) (MD 1.90 g/dL, 95% CI 1.66 to 2.14), haematocrit (HCT) (MD 27.10%, 95% CI 26.49 to 27.71), change in albumin (MD 4.91 g/L, 95% CI 3.69 to 6.13), alanine aminotransferase (ALT) (MD 54.50 U/L, 95% CI 43.94 to 65.06), and aspartate aminotransferase (AST) (MD 47.33 U/L, 95% CI 37.69 to 56.97); and decrease high-density lipoprotein (HDL) (MD -15.66 mg/dL, 95% CI -24.84 to -6.48). We also found that compared with erythropoietin alone, nandrolone decanoate plus erythropoietin may increase HCT (3 studies, 73 participants: MD 2.54%, 95% Cl 0.96 to 4.12). Compared with erythropoietin (1 study, 27 participants), limited evidence was found to suggest that nandrolone decanoate can increase plasma total protein (MD 0.40 g/L, 95% CI 0.13 to 0.67), albumin (MD 0.20 g/L, 95% CI 0.01 to 0.39), and transferrin (MD 45.00 mg/dL, 95% CI 12.61 to 77.39) levels. Compared with no therapy (remnant kidney), evidence was found to suggest that nandrolone decanoate can increase Hb (2 studies, 33 participants: MD 1.04 g/dL, 95% Cl 0.66 to 1.41) and HCT (1 study, 24 participants: MD 3.70%, 95% Cl 0.68 to 6.72). Compared with no therapy (anephric), evidence was found (1 study, 5 participants) to suggest that nandrolone decanoate can increase Hb (MD 1.30 g/dL, 95% Cl 0.57 to 2.03), but nandrolone decanoate did not increase HCT (MD 2.00%, 95% Cl -0.85 to 4.85).However, oxymetholone was not found to reduce blood urea nitrogen (BUN), serum creatinine (SCr), cholesterol, or triglycerides; or increase plasma total protein, prealbumin, or transferrin. No evidence was found to indicate that nandrolone decanoate increased prealbumin or decreased BUN, SCr, AST, ALT, cholesterol, triglycerides, HDL or low-density lipoprotein (LDL). Adverse events associated with androgen therapy were reported infrequently.
AUTHORS' CONCLUSIONS
We found insufficient evidence to confirm that use of androgens for adults with CKD-related anaemia is beneficial.
Topics: Adult; Androgens; Anemia; Cholesterol; Erythropoietin; Hematocrit; Humans; Nandrolone; Nandrolone Decanoate; Oxymetholone; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Triglycerides
PubMed: 25300168
DOI: 10.1002/14651858.CD006881.pub2 -
Best Practice & Research. Clinical... Jun 2014Anaemia is a common finding at diagnosis in myelofibrosis, and becomes a symptomatic problem in most patients with time. There are several treatment options for specific... (Review)
Review
Anaemia is a common finding at diagnosis in myelofibrosis, and becomes a symptomatic problem in most patients with time. There are several treatment options for specific anaemia treatment, none of which has been tested in large, randomized, controlled trials. However, as myelofibrosis is not a disease with spontaneous remissions, even non-randomized trials carry weight. In this survey, the existing evidence will be analysed, both for the commonly used treatments like erythropoiesis-stimulating agents, androgens and thalidomide and for the new drugs in the area, and conclusions will be drawn concerning standard clinical anaemia treatment in myelofibrosis, which according to evidence from studies has a 40-50% chance of response in patients with not too advanced disease.
Topics: Androgens; Anemia; Blood Transfusion; Erythropoietin; Hematinics; Humans; Immunosuppressive Agents; Interferons; Lenalidomide; Nitriles; Oxymetholone; Primary Myelofibrosis; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Thalidomide
PubMed: 25189728
DOI: 10.1016/j.beha.2014.07.011 -
Avicenna Journal of Phytomedicine Jan 2014Objectives : The aim of the present study was to evaluate protective effect of royal jelly on sperm parameters, testosterone level, and malondialdehyde (MDA) production...
UNLABELLED
Objectives : The aim of the present study was to evaluate protective effect of royal jelly on sperm parameters, testosterone level, and malondialdehyde (MDA) production in mice.
MATERIALS AND METHODS
Thirty-two adult male NMRI mice weighing 30±2 g were used. All the animals were divided into 4 groups.
CONTROL GROUP
received saline 0.1 ml/mouse/day orally for 30 days. Royal jelly group (RJ): received royal jelly at dose of 100 mg/kg daily for 30 days orally. Oxymetholone group: the received Oxymetholone (OX) at dose of 5 mg/kg daily for 30 days orally. Royal jelly+Oxymetholone group: received royal jelly at dose of 100 mg/kg/day orally concomitant with OX administration. Sperm count, sperm motility, viability, maturity, and DNA integrity were analyzed. Furthermore, serum testosterone and MDA concentrations were determined.
RESULTS
In Oxymetholone group, sperm count, motility as well as testosterone concentration reduced significantly (p<0.05), while significant (p<0.05) increases in immature sperm, sperm with DNA damaged, and MDA concentration were announced in Oxymetholone group in comparison with control group and Royal jelly+Oxymetholone group. RJ caused partially amelioration in all of the above- mentioned parameters in Royal Jelly+Oxymetholone group.
CONCLUSION
In conclusion, RJ may be used in combination with OX to improve OX-induced oxidative stress and male infertility.
PubMed: 25050300
DOI: No ID Found -
Talanta Apr 2014A new chemically modified electrode was constructed and applied to the electro-oxidation of the oxymetholone. Also, the electrode was applied to the simple, rapid,...
A new chemically modified electrode was constructed and applied to the electro-oxidation of the oxymetholone. Also, the electrode was applied to the simple, rapid, highly selective and sensitive determination of oxymetholone (OXM) in pharmaceutical and plasma samples using square wave voltammetry (SWV). The multi-walled carbon nanotubes modified glassy carbon electrode (MWCNT/GCE) were prepared by casting of the multi-walled carbon nanotubes (MWCNT) suspension on the glassy carbon electrode surface. The limit of detection and the linear range were found to be 1.36 and 2.00-90.00 ng mL(-1) of OXM, respectively. The effects of potentially interfering substances on the determination of this compound were investigated and found that the electrode is highly selective. The proposed modified electrode was used for the determination of OXM in human plasma and pharmaceutical samples. This reveals that MWCNT/GCE shows excellent analytical performance for the determination of OXM in terms of very low detection limit, high sensitivity, very good repeatability and reproducibility over other methods reported in literature.
PubMed: 24607102
DOI: 10.1016/j.talanta.2013.12.047 -
QJM : Monthly Journal of the... Aug 2014
Topics: Adult; Anabolic Agents; Humans; Infarction; Kidney; Male; Oxymetholone; Performance-Enhancing Substances; Polycythemia; Substance-Related Disorders; Tomography, X-Ray Computed; Weight Lifting
PubMed: 24557731
DOI: 10.1093/qjmed/hcu042 -
Talanta Oct 2013A novel and sensitive extraction procedure using maghemite nanoparticles (γ-Fe2O3) modified with sodium dodecyl sulfate (SDS), as an efficient solid phase, was...
Preconcentration and spectrophotometric determination of oxymetholone in the presence of its main metabolite (mestanolone) using modified maghemite nanoparticles in urine sample.
A novel and sensitive extraction procedure using maghemite nanoparticles (γ-Fe2O3) modified with sodium dodecyl sulfate (SDS), as an efficient solid phase, was developed for removal, preconcentration and spectrophotometric determination of trace amounts of oxymetholone (OXM), in the presence of mestanolone (MSL). Combination of nanoparticle adsorption and easily magnetic separation was used for the extraction and desorption of OXM. The preparation of γ-Fe2O3 nanoparticles were obtained by co-precipitation method and their surfaces were modified by SDS. The size and properties of the produced γ-Fe2O3 nanoparticles were determined by X-ray diffraction analysis, FT-IR and scanning electron microscopy measurements. OXM and MSL became adsorbed at pH 3.0. The adsorbed drugs were then desorbed and determined spectrophotometrically using a selective complexation reaction for OXM. The calibration graph was linear in the range 15.0-3300.0 ng mL(-1) of OXM with a correlation coefficient of 0.9948. The detection limit of the method for determination of OXM was 4.0 ng mL(-1). The method was applied for the determination of OXM in human urine samples.
Topics: Androgens; Calibration; Dihydrotestosterone; Ferric Compounds; Humans; Hydrogen-Ion Concentration; Limit of Detection; Magnetite Nanoparticles; Microscopy, Electron, Scanning; Oxymetholone; Particle Size; Scattering, Small Angle; Sodium Dodecyl Sulfate; Solid Phase Extraction; Spectrophotometry; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction
PubMed: 24054620
DOI: 10.1016/j.talanta.2013.05.056 -
Pediatric Blood & Cancer Jan 2014A majority of Fanconi anemia (FA) patients will experience bone marrow failure (BMF) and androgen therapy (most often oxymetholone) may be utilized as a treatment to...
BACKGROUND
A majority of Fanconi anemia (FA) patients will experience bone marrow failure (BMF) and androgen therapy (most often oxymetholone) may be utilized as a treatment to improve BMF-related cytopenias. However, oxymetholone is associated with toxicities making identification of other agents of interest. In this study we aimed to evaluate the toxicity profile and hematologic response in patients with FA who are treated with low-dose oxandrolone, a synthetic non-fluorinated anabolic steroid, similar to oxymetholone, with known dosing thresholds for virilization.
PROCEDURE
A single arm, Phase I/II study was designed to treat patients on low-dose oxandrolone. If no toxicity or hematologic response was noted at 16 weeks, a single dose escalation was offered. Subjects were regularly assessed for toxicity, including determinations of virilization, behavioral changes, and liver and kidney function. At 32 weeks, those who demonstrated hematologic response were allowed to continue study treatment, and those without improvement were deemed non-responsive.
RESULTS
Nine subjects completed the study and were followed for a median of 99 weeks (46-136 weeks). Three (33.3%) subjects developed mild sub-clinical virilization and continued treatment with a dose reduction. None (0%) had adverse behavioral changes. Two (22.2%) developed elevated liver function tests at 42 and 105 weeks. Seven (77.8%) subjects had a hematologic response.
CONCLUSION
Oxandrolone appears to be well-tolerated, has limited toxicities at the administered doses in FA with patients, and may be an alternative androgen for the treatment of BMF in FA.
Topics: Anabolic Agents; Anemia, Aplastic; Bone Marrow Diseases; Bone Marrow Failure Disorders; Child; Fanconi Anemia; Female; Hemoglobinuria, Paroxysmal; Humans; Male; Oxandrolone
PubMed: 24019220
DOI: 10.1002/pbc.24617 -
Chemistry Central Journal Dec 2012Biotransformation of organic compounds by using microbial whole cells provides an efficient approach to obtain novel analogues which are often difficult to synthesize...
BACKGROUND
Biotransformation of organic compounds by using microbial whole cells provides an efficient approach to obtain novel analogues which are often difficult to synthesize chemically. In this manuscript, we report for the first time the microbial transformation of a synthetic anabolic steroidal drug, oxymetholone, by fungal cell cultures.
RESULTS
Incubation of oxymetholone (1) with Macrophomina phaseolina, Aspergillus niger, Rhizopus stolonifer, and Fusarium lini produced 17β-hydroxy-2-(hydroxy-methyl)-17α-methyl-5α-androstan-1-en-3-one (2), 2α,17α-di(hydroxyl-methyl)-5α-androstan-3β,17β-diol (3), 17α-methyl-5α-androstan-2α,3β,17β-triol (4), 17β-hydroxy-2-(hydroxymethyl)-17α-methyl-androst-1,4-dien-3-one (5), 17β-hydroxy-2α-(hydroxy-methyl)-17α-methyl-5α-androstan-3-one (6), and 2α-(hydroxymethyl)-17α-methyl-5α-androstan-3β-17β-diol (7). Their structures were deduced by spectral analyses, as well as single-crystal X-ray diffraction studies. Compounds 2-5 were identified as the new metabolites of 1. The immunomodulatory, and anti-inflammatory activities and cytotoxicity of compounds 1-7 were evaluated by observing their effects on T-cell proliferation, reactive oxygen species (ROS) production, and normal cell growth in MTT assays, respectively. These compounds showed immunosuppressant effect in the T-cell proliferation assay with IC50 values between 31.2 to 2.7 μg/mL, while the IC50 values for ROS inhibition, representing anti-inflammatory effect, were in the range of 25.6 to 2.0 μg/mL. All the compounds were found to be non-toxic in a cell-based cytotoxicity assay.
CONCLUSION
Microbial transformation of oxymetholone (1) provides an efficient method for structural transformation of 1. The transformed products were obtained as a result of de novo stereoselective reduction of the enone system, isomerization of double bond, insertion of double bond and hydroxylation. The transformed products, which showed significant immunosuppressant and anti-inflammatory activities, can be further studied for their potential as novel drugs.
PubMed: 23237028
DOI: 10.1186/1752-153X-6-153