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Journal of Food Biochemistry Sep 2022Misuse and abuse of anabolic androgenic steroids (AAS) such as oxymetholone (OM) cause side effects such as male infertility, cardiovascular disorders, musculoskeletal,...
Misuse and abuse of anabolic androgenic steroids (AAS) such as oxymetholone (OM) cause side effects such as male infertility, cardiovascular disorders, musculoskeletal, and hepato-renal dysfunctions in athletes. The aim of this study was to evaluate the protective effects of Lepidium draba L. (L. draba) extract on OM-induced hepato-renal toxicity. Thirty adult male Wistar rats into six groups (n = 5) were randomly divided as follows: control (normal saline), OM (5 mg/kg/day), L. draba-treated (100, 200, and 400 mg/kg/d) plus 5 mg/kg/day OM, and L. draba (400 mg/kg/d) groups. Normal saline, OM and L. draba extract were orally administered for 30 days. On day 31 of the study, hepatic and renal biochemical parameters were measured. Serum cytokines (IL-1β, IL-10, IL-6) tumor necrosis factor- α (TNF-α) and nitric oxide, levels alongside catalase, glutathione peroxidase, and superoxide dismutase activity were evaluated. Also, changes in liver and kidney histopathology were evaluated. Finally, the anti-oxidant properties of the extract were determined. The results of this study showed that in the groups treated with the L. draba extract, hepatic-renal biochemical parameters improved and also the level of nitric oxide and inflammatory cytokines decreased and the activity of anti-oxidant enzymes increased compared with the OM group. These findings revealed that L. draba, due to its high anti-oxidant properties and high content of polyphenols (especially flavonoids), can improve OM-induced hepato-renal oxidative damages. PRACTICAL APPLICATIONS: L. draba due to its remarkable anti-oxidant and anti-inflammatory properties can protects the kidney and liver injuries against oxymetholone. These features are attributed to the presence of phenolic and flavonoid components. This fidings would be helpful to desgin new therapeutic agents for treating and preventing liver/kidney injuries.
Topics: Animals; Antioxidants; Cytokines; Lepidium; Male; Nitric Oxide; Oxidative Stress; Oxymetholone; Plant Extracts; Rats; Rats, Wistar; Saline Solution
PubMed: 35633194
DOI: 10.1111/jfbc.14250 -
Andrologia Dec 2021This study was aimed to investigate the protective effects of Lepidium draba L. (L. draba) extract on oxymetholone (OM)-induced testicular injury in rat. Six groups of...
Protective effects of Lepidium draba L. leaves extract on testis histopathology, oxidative stress indicators, serum reproductive hormones and inflammatory signalling in oxymetholone-treated rat.
This study was aimed to investigate the protective effects of Lepidium draba L. (L. draba) extract on oxymetholone (OM)-induced testicular injury in rat. Six groups of n = 5 adult male rats were used as; 1: control, 2: OM (5 mg/kg OM orally), 3, 4 and 5: L. draba extract (100, 200 and 400 mg kg day ) +OM (5 mg kg day OM) and 6:400 mg/kg/d L. draba extract for 30 days. Serum testosterone (T), follicle-stimulating hormone (FSH) and luteinising hormone (LH), inflammatory cytokines (IL-6, IL-10, TNF-α, IL-1β), oxidative stress (OS) indicators [superoxide dismutase, catalase, glutathione peroxidase and nitric oxide (NO)], apoptotic related genes (Bcl-2, p53, caspase-3 (c3) and Bax) were investigated. OM significantly increased the serum levels of T, proinflammatory cytokines and pro-apoptotic genes expression. Also, it decreased LH and FSH, sperm viability, count and motility. L. draba extract especially could markedly normalise the serum levels of LH and FSH, and T, restore serum antioxidant enzymes and suppressed the pro-inflammatory cytokines. Also, germ cells apoptosis was inhibited against via downregulating the p53, c3, Bax and upregulating Bcl-2. It concluded that L. draba extract could protect the function and structure of testis against OM-induced testicular toxicity via its antioxidant and anti-inflammatory properties.
Topics: Animals; Lepidium; Luteinizing Hormone; Oxidative Stress; Oxymetholone; Plant Extracts; Plant Leaves; Rats; Testis
PubMed: 34520070
DOI: 10.1111/and.14239 -
Foods (Basel, Switzerland) Apr 2021In recent years, the undeclared presence of various anabolic androgenic steroids (AAS) in commercial supplements has been confirmed. This fact can be a potential threat...
In recent years, the undeclared presence of various anabolic androgenic steroids (AAS) in commercial supplements has been confirmed. This fact can be a potential threat to all athletes using these supplements, and therefore, there is of increased interest in the implementation of rapid methods for the detection of AAS. The presented study describes the development of an immunostrip test for the detection of multiple 17α-methylated AAS based on direct and indirect competitive principle using gold nanoparticles as a label. As a capture reagent on test lines conjugated stanazolol to rabbit serum albumin (RSA/ST-3) was used, the intensity of color formed in the test line of the AAS-positive sample was visually distinguishable from that of negative sample within 10 min. The optimized closed direct and indirect format of the test provided a similar visual detection limit (0.7 and 0.9 ng/mL, respectively). The most commonly orally abused AAS (17α-methyltestosterone, methandienone, methyldihydrotestosterone, oxandrolone and oxymetholone) showed a strong cross-reaction. Developed immunostrips were successfully applied to analysis of artificially contaminated dietary supplements with 17α-methylated AASs. The developed immunostrips offer potential as a useful user-friendly method for capturing suspicious dietary supplement samples with different contents of AAS at levels far below the usually used concentrations of AAS.
PubMed: 33915816
DOI: 10.3390/foods10040741 -
Journal of Pediatric Hematology/oncology Jan 2022Fanconi aplastic anemia (FAA) is a rare inherited bone marrow failure disorder characterized by congenital defects and pancytopenia. Hematopoietic stem cell...
Fanconi aplastic anemia (FAA) is a rare inherited bone marrow failure disorder characterized by congenital defects and pancytopenia. Hematopoietic stem cell transplantation (HSCT) is a curative treatment for patients with FAA due to the risk of cancer and pancytopenia. Blood transfusions are the best supportive therapy. Oxymetholone (5 mg/kg daily) is most commonly used; however, it is not curative. Extensive transfusions should be avoided because of alloimmunization and graft-versus-host disease because they have poor outcomes in patients with HSCT. This is a case report of a 5-year-old Syrian male patient with FAA, who was successfully treated with eltrombopag (50 mg daily) in conjunction with oxymetholone (5 mg/kg daily). The patient required platelet transfusions despite oxymetholone therapy and there was no suitable donor for HSCT. After the addition of eltrombopag therapy, platelet transfusions were no longer required. Eltrombopag can be effectively used as a bridge to HSCT in patients with FAA.
Topics: Allografts; Benzoates; Child, Preschool; Fanconi Anemia; Hematopoietic Stem Cell Transplantation; Humans; Hydrazines; Male; Pyrazoles
PubMed: 33560087
DOI: 10.1097/MPH.0000000000002082 -
International Journal of Molecular... Sep 2020Dyskeratosis congenita (DKC) is a rare inherited disease of impaired telomere maintenance that progressively leads to multi-organ failure, including the bone marrow. By...
Comparable Effects of the Androgen Derivatives Danazol, Oxymetholone and Nandrolone on Telomerase Activity in Human Primary Hematopoietic Cells from Patients with Dyskeratosis Congenita.
Dyskeratosis congenita (DKC) is a rare inherited disease of impaired telomere maintenance that progressively leads to multi-organ failure, including the bone marrow. By enhancing telomerase activity, androgen derivatives (ADs) are a potential therapeutic option able to re-elongate previously shortened telomeres. Danazol, oxymetholone, and nandrolone are ADs most frequently used to treat DKC. However, no direct in vitro analyses comparing the efficacy of these ADs have been conducted so far. We therefore treated mononuclear cells derived from peripheral blood and bone marrow of four patients with mutations in telomerase reverse transcriptase (, = 1),in the telomerase RNA component (TERC, = 2) and in dyskerin pseudouridine synthase 1 (, = 1) and found no substantial differences in the activity of these three agents in patients with mutations. All AD studied produced comparable improvements of proliferation rates as well as degrees of telomere elongation. Increased expression levels were shown with danazol and oxymetholone. The beneficial effects of all ADs on proliferation of bone marrow progenitors could be reversed by tamoxifen, an estrogen antagonist abolishing estrogen receptor-mediated expression, thereby underscoring the involvement of in AD mechanism of action. In conclusion, no significant differences in the ability to functionally enhance telomerase activity could be observed for the three AD studied in vitro. Physicians therefore might choose treatment based on patients' individual co-morbidities, e.g., pre-existing liver disease and expected side-effects.
Topics: Androgens; Cell Cycle Proteins; Danazol; Dyskeratosis Congenita; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Mutation; Nandrolone; Nuclear Proteins; Oxymetholone; Primary Cell Culture; RNA; Telomerase; Telomere
PubMed: 33003434
DOI: 10.3390/ijms21197196 -
Drug Testing and Analysis Sep 2020Anabolic androgenic steroids (AASs) comprise a class of synthetic androgens resulting from chemical modifications of testosterone, known for their illicit consumption,... (Comparative Study)
Comparative Study
Anabolic androgenic steroids (AASs) comprise a class of synthetic androgens resulting from chemical modifications of testosterone, known for their illicit consumption, which can result inextensive side effects. Extraction procedures applied to the analysis of their formulations are still limited to a few methodologies, despite the increasing numbers of confiscations of AASs. In this sense, the aims of this work were to evaluate the extraction of active ingredients from formulations of anabolic agents using solid-liquid or liquid-iquid, ultrasonic bath, ultrasonicprobe, and microwave-assisted extraction. The results indicated that the extraction procedures influenced the detected concentration of AASs, as the use of ultrasonic probe and microwave irradiation increased the overall extraction of anabolic agents compared with solid-liquid, liquid-liquid, and ultrasonic bath. Regarding oxymetholone, for instance, the microwave-assisted extraction and ultrasonic probe extracted, respectively, 37.46 ± 1.36 and 35.69 ± 0.98 mg/tablet, while solid-liquid extracted 29.63 ± 0.40 mg/tablet of the activeingredient. Therefore, alternative methods such as microwave-assisted extraction or theultrasonic probe could be used for the analysis of formulations of AASs assisting with the identification of illicit and toxic components.
Topics: Anabolic Agents; Chemical Fractionation; Doping in Sports; Liquid-Liquid Extraction; Microwaves; Solid Phase Extraction; Tablets; Testosterone Congeners; Ultrasonics
PubMed: 32537903
DOI: 10.1002/dta.2877 -
British Journal of Haematology Jun 2020Progressive cytopenia is a serious complication among paediatric patients with inherited bone marrow failure syndromes (IBMFS). Androgens have been used to improve blood...
Progressive cytopenia is a serious complication among paediatric patients with inherited bone marrow failure syndromes (IBMFS). Androgens have been used to improve blood counts in different bone marrow failure conditions. Little is known about efficacy and toxicity with new androgens (i.e., danazol) in different types of IBMFS. We identified 29 patients from the Canadian Inherited Marrow Failure Registry, who received oxymetholone or danazol. Sixteen (55%) had haematological response including patients with unclassified IBMFS (45%). Danazol showed a better toxicity profile and similar efficacy compared to oxymetholone. Androgens are an effective and safe option to ameliorate bone marrow failure in IBMFS.
Topics: Adolescent; Adult; Androgens; Bone Marrow Failure Disorders; Canada; Cell Lineage; Child; Child, Preschool; Combined Modality Therapy; Danazol; Disease Progression; Drug Substitution; Female; Hematopoietic Stem Cell Transplantation; Humans; Infant; Male; Middle Aged; Oxymetholone; Pancytopenia; Registries; Thrombocytopenia; Treatment Outcome; Virilism
PubMed: 32128787
DOI: 10.1111/bjh.16445 -
Andrologia Apr 2020Anabolic androgenic steroids (AAS) such as oxymetholone (OM) used for athletic enhancement, but increased free radicals damage and changes in hormonal levels, lead to...
The effects of hydroalcoholic extract of Vaccinium arctostaphylos L. on sperm parameters, oxidative injury and apoptotic changes in oxymetholone-induced testicular toxicity in mouse.
Anabolic androgenic steroids (AAS) such as oxymetholone (OM) used for athletic enhancement, but increased free radicals damage and changes in hormonal levels, lead to serious and irreversible organ damage. Vaccinium arctostaphylos(V. arctostaphylos( has been demonstrated to have antioxidant and antiinflammatory effects. The aim of present study was to investigate V. arctostaphylos effect on OM-induced oxidative injury in mouse testis and sperm parameters. In this experimental study, 30 BALB/c mice were divided into five groups, including healthy, positive control(5 mg/kg OM) and three treatment groups (100, 200 and 400 mg/kg of V. arctostaphylos extract + 5 mg/kg OM). At the end of the study, serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone levels were measured. Testis stereological and sperm parameters were calculated. Antioxidant status was measured using nitric oxide (NO) and FRAP assay, and malondialdehyde (MDA) levels. Furthermore, the expression of p53, caspase-3, Bax and Bcl-2 was measured. V. arctostaphylos decreased the serum level of testosterone, increased the LH and FSH, and improved the stereological and sperm parameters and down-regulated the p53, caspase-3 and Bax and up-regulated Bcl-2 genes. Furthermore, this dose decreased serum levels of NO and increased testis FRAP and MDA levels in treated groups compared with OM group. V. arctostaphylos extract has protective effects against testicular toxicity caused by OM.
Topics: Animals; Apoptosis; Cell Survival; Disease Models, Animal; Ethanol; Fruit; Humans; Infertility, Male; Male; Mice; Oxidative Stress; Oxymetholone; Plant Extracts; Protective Agents; Sperm Count; Sperm Motility; Testis; Vaccinium; Water
PubMed: 32012329
DOI: 10.1111/and.13522 -
Biochemical Pharmacology Feb 2020Anabolic-androgenic steroids (AAS) are testosterone derivatives developed for steroid-replacement and treatment of debilitating conditions. They are widely used by...
Anabolic-androgenic steroids (AAS) are testosterone derivatives developed for steroid-replacement and treatment of debilitating conditions. They are widely used by athletes in elite sports and bodybuilding due to their muscle-building and performance-enhancing properties. Excessive AAS use is associated with cardiovascular diseases, mood changes, endocrine and metabolic disorders; however, the underlying mechanisms remain unknown. Selective androgen receptor modulators (SARMs) aim to reduce adverse androgenic effects, while maximizing anabolic effects. This study assessed potential steroidogenic disturbances of 19 AAS and 3 SARMs in human adrenocortical carcinoma H295R cells, comparing basal and forskolin-activated states by mass spectrometry-based quantification of nine major adrenal steroids. Mesterolone, mestanolone and methenolone increased mineralocorticoid but decreased adrenal androgen production, indicating CYP17A1 dysfunction. Cell-free activity assays failed to detect direct CYP17A1 inhibition, supported by molecular modeling. The mRNA expression levels of 3β-HSD2, CYP17A1, CYP21A2, CYP11B1 and CYP11B2 were unaffected, suggesting indirect inhibition involving post-translational modification and/or impaired protein stability. Clostebol and oxymetholone decreased corticosteroid but increased dehydroepiandrosterone biosynthesis in H295R cells, suggesting CYP21A2 inhibition, sustained by molecular modeling. These AAS did not affect the expression of key steroidogenic genes. None of the SARMs tested interfered with steroidogenesis. The chosen approach allowed the grouping of AAS according to their steroidogenic-disrupting effects and provided initial mechanistic information. Mesterolone, mestanolone and methenolone potentially promote hypertension and cardiovascular diseases via excessive mineralocorticoid biosynthesis. Clostebol and oxymetholone might cause metabolic disturbances by suppressing corticosteroid production, resulting in adrenal hyperplasia. The non-steroidal SARMs exhibit an improved safety profile and represent a preferred therapeutic option.
Topics: Adrenal Gland Neoplasms; Adrenal Glands; Anabolic Agents; Androgens; Cell Line, Tumor; Cell Survival; Cytochrome P-450 Enzyme System; Gene Expression Regulation; Humans
PubMed: 31884045
DOI: 10.1016/j.bcp.2019.113781