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Iranian Biomedical Journal Sep 2016The present study was carried out to investigate the possible protective effects of royal jelly (RJ) on oxymetholone (OXM)-induced oxidative liver injuries in mice.
BACKGROUND
The present study was carried out to investigate the possible protective effects of royal jelly (RJ) on oxymetholone (OXM)-induced oxidative liver injuries in mice.
METHODS
In total, 32 adult male NMRI mice were divided into four groups of eight mice each. Mice in groups 1 and 2 were orally administered 5 mg/kg/day OXM for 30 days. At the same time, mice in group 3 received RJ at a dose of 100 mg/kg/day. Saline control and RJ control groups were also included in this study.
RESULTS
Administration of 5 mg/kg OXM resulted in a significant decrease in total antioxidant capacity and catalase activity, as well as a significant increase in malondialdehyde (P<0.05). In addition, OXM-administrated mice showed a slight increase in liver enzymes, including alanine amino transferase, aspartate amino transferase, and alkaline phosphatase. Although OXM caused histopathological changes in the liver, RJ could significantly improve all of the above-mentioned parameters at a dose of 100 mg/kg.
CONCLUSION
The results of the present study indicated that RJ has a partially protective effect on OXM-induced liver toxicity in mice.
Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Antioxidants; Aspartate Aminotransferases; Catalase; Fatty Acids; Liver; Male; Malondialdehyde; Mice; Oxidative Stress; Oxymetholone
PubMed: 27178489
DOI: 10.7508/ibj.2016.04.007 -
Cell Journal 2015This study aimed to investigate the effects of royal jelly (RJ) on catalase, total antioxidant capacity and embryo development in adult mice treated with oxymetholone...
OBJECTIVE
This study aimed to investigate the effects of royal jelly (RJ) on catalase, total antioxidant capacity and embryo development in adult mice treated with oxymetholone (OXM).
MATERIALS AND METHODS
In this exprimental study, 32 male and 96 female adult Naval Medical Research Institute (NMRI) mice (7-9 weeks of age) with a ratio of 1:3 for fertili- zation purposes were randomly divided into 4 groups as follows: i. Control group (n=8) receiving 0.1 ml/mice saline daily by gavage for 30 day, ii. RJ group (n=8) treated with RJ at a dose of 100 mg/kg daily by gavage for 30 days, iii. OXM group (n=8) receiving OXM at the dose of 5 mg/kg daily by gavage for 30 days and iv. RJ+OXM group (n=8) receiving RJ at the dose of 100 mg/kg daily by gavage concomitant with 100 mg/kg OXM adminis- tration for 30 days.
RESULTS
Analysis revealed a significant reduction in catalase, total antioxidant, as well as embryo development in OXM group (P<0.05). However, RJ group showed a salient recovery in the all of the above mentioned parameters and embryo toxicity.
CONCLUSION
The results of this study indicated a partially protective effect of RJ against OXM-induced embryo toxicity.
PubMed: 26464831
DOI: 10.22074/cellj.2015.19 -
Oxidative Medicine and Cellular... 2015The objective of this study was to assess the possible beneficial skeletal muscle preserving effects of ethanol extract of Schisandrae Fructus (EESF) on sciatic...
The objective of this study was to assess the possible beneficial skeletal muscle preserving effects of ethanol extract of Schisandrae Fructus (EESF) on sciatic neurectomy- (NTX-) induced hindlimb muscle atrophy in mice. Here, calf muscle atrophy was induced by unilateral right sciatic NTX. In order to investigate whether administration of EESF prevents or improves sciatic NTX-induced muscle atrophy, EESF was administered orally. Our results indicated that EESF dose-dependently diminished the decreases in markers of muscle mass and activity levels, and the increases in markers of muscle damage and fibrosis, inflammatory cell infiltration, cytokines, and apoptotic events in the gastrocnemius muscle bundles are induced by NTX. Additionally, destruction of gastrocnemius antioxidant defense systems after NTX was dose-dependently protected by treatment with EESF. EESF also upregulated muscle-specific mRNAs involved in muscle protein synthesis but downregulated those involved in protein degradation. The overall effects of 500 mg/kg EESF were similar to those of 50 mg/kg oxymetholone, but it showed more favorable antioxidant effects. The present results suggested that EESF exerts a favorable ameliorating effect on muscle atrophy induced by NTX, through anti-inflammatory and antioxidant effects related to muscle fiber protective effects and via an increase in protein synthesis and a decrease in protein degradation.
Topics: Animals; Antioxidants; Body Weight; Creatine Kinase; Cytokines; Dietary Supplements; Ethanol; Fruit; Immunohistochemistry; L-Lactate Dehydrogenase; Male; Mice; Mice, Inbred ICR; Muscle Strength; Muscle, Skeletal; Muscular Atrophy; Plant Extracts; Schisandra; Sciatic Nerve
PubMed: 26064425
DOI: 10.1155/2015/872428 -
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 -
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 -
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 -
Clinical Journal of the American... Feb 2013Sarcopenia is common in hemodialysis patients. This study examined whether the anabolic steroid oxymetholone improves muscle mass and handgrip strength in hemodialysis... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND OBJECTIVES
Sarcopenia is common in hemodialysis patients. This study examined whether the anabolic steroid oxymetholone improves muscle mass and handgrip strength in hemodialysis patients and possible mechanisms that might engender such changes.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
Forty-three eligible hemodialysis patients were randomly assigned to ingest oxymetholone or placebo for 24 weeks. Body composition, handgrip strength, and quality of life were measured during the study. Muscle biopsies were performed and analyzed for mRNA levels for myostatin, IGF-I, IGF binding proteins, and myosin heavy chains and protein expression. Muscle fiber types and diameter were assessed by reduced nicotinamide-adenine dinucleotide staining.
RESULTS
There was a significantly greater increase in fat-free mass and handgrip strength and decrease in fat mass in the oxymetholone compared with the placebo group. Moreover, compared with baseline values, patients given oxymetholone exhibited an increase in fat-free mass, handgrip strength, physical functioning scores, and type I muscle fiber cross-sectional area and a decrease in fat mass, whereas patients receiving placebo did not undergo changes. There was a significantly greater increase in muscle mRNA levels for myosin heavy chain 2×, IGF-I, and IGF-II receptor with oxymetholone treatment than placebo. Liver enzyme rose significantly in the oxymetholone group, but the number of values greater than three times the upper limit of normal were not different between these groups.
CONCLUSIONS
In hemodialysis patients, ingesting oxymetholone was associated with an increase in fat-free mass, handgrip strength, and muscle mRNA levels for several growth factors and a decrease in fat mass, but it also induced liver injury.
Topics: Administration, Oral; Adult; Anabolic Agents; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscle Strength; Muscle, Skeletal; Oxymetholone; Renal Dialysis
PubMed: 23124786
DOI: 10.2215/CJN.00380112 -
Report on Carcinogens : Carcinogen... 2011
Topics: Androgens; Animals; Carcinogenicity Tests; Carcinogens, Environmental; Government Regulation; Guidelines as Topic; Humans; Leukemia; Molecular Structure; Neoplasms; Occupational Exposure; Oxymetholone; Rats
PubMed: 21860526
DOI: No ID Found