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Environmental Health Perspectives Oct 1999In vivo carcinogenicity testing is an expensive and time-consuming process, and as a result, only a relatively small fraction of new and existing chemicals has been...
In vivo carcinogenicity testing is an expensive and time-consuming process, and as a result, only a relatively small fraction of new and existing chemicals has been tested in this manner. Therefore, the development and validation of alternative approaches is desirable. We previously developed a mammalian in vitro assay for genotoxicity based on the ability of cells to increase their level of the tumor-suppressor protein p53 in response to DNA damage. Cultured cells are treated with various amounts of the test substances, and at defined times following treatment, they are harvested and lysed. The lysates are analyzed for p53 by Western blot and/or enzyme-linked immunosorbent assay analysis. An increase in cellular p53 following treatment is interpreted as evidence for DNA damage. To determine the ability of this p53-induction assay to predict carcinogenicity in rodents and to compare such results with those obtained using alternate approaches, we subjected 25 chemicals from the predictive toxicology evaluation 2 list to analysis with this method. Five substances (citral, cobalt sulfate heptahydrate, D&C Yellow No. 11, oxymetholone, and t-butylhydroquinone) tested positive in this assay, and three substances (emodin, phenolphthalein, and sodium xylenesulfonate) tested as possibly positive. Comparisons between the results obtained with this assay and those obtained with the in vivo protocol, the Salmonella assay, and the Syrian hamster embryo (SHE) cell assay indicate that the p53-induction assay is an excellent predictor of the limited number of genotoxic carcinogens in this set, and that its accuracy is roughly equivalent to or better than the Salmonella and SHE assays for the complete set of chemicals.
Topics: Acyclic Monoterpenes; Animals; Carcinogenicity Tests; Carcinogens; Cell Line; Cobalt; Cricetinae; Mesocricetus; Mice; Monoterpenes; Mutagens; Terpenes; Tumor Suppressor Protein p53
PubMed: 10504146
DOI: 10.1289/ehp.99107805 -
Hormones and Behavior Feb 1997Six separate experiments were conducted which examined the effects of long-term administration of anabolic-androgenic steroid (AAS) compounds on the sexual behavior of...
Six separate experiments were conducted which examined the effects of long-term administration of anabolic-androgenic steroid (AAS) compounds on the sexual behavior of gonadally intact male rats. The six AAS compounds analyzed in this study were 17alpha-methyltestosterone, methandrostenolone, nandrolone decanoate, stanozolol, oxymetholone, and testosterone cypionate. In each experiment, subjects received daily injections of a high, medium, or low dose of the AAS compound, or the oil vehicle, for 12 weeks. Sexual behavior was quantified weekly. Twelve weeks of administration of the high dose of three AAS compounds, 17alpha-methyltestosterone, stanozolol, and oxymetholone, eliminated male sexual behavior. These treatments also suppressed serum testosterone levels. The remaining compounds had minimal effects on sexual behavior at any dose. Thus, in intact male rats the six AAS compounds examined in these studies evoked a range of behavioral and endocrine responses that varied as a function of the specific compound and dose administered.
Topics: Androgens; Animals; Body Weight; Male; Oxymetholone; Rats; Sexual Behavior, Animal; Stanozolol
PubMed: 9109597
DOI: 10.1006/hbeh.1997.1355 -
Journal of the International Society of... Oct 2018A proprietary composition GMCT contains extracts of two popular Asian herbs viz., Garcinia mangostana (GM) fruit rind and Cinnamomum tamala (CT) leaf. We systematically... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
A proprietary composition GMCT contains extracts of two popular Asian herbs viz., Garcinia mangostana (GM) fruit rind and Cinnamomum tamala (CT) leaf. We systematically evaluated physical performance and muscle strength enhancing ability of GMCT in a preclinical mouse model followed by a 42-days double-blind placebo controlled human trial in resistance trained adult males.
METHODS
Four groups of Swiss albino mice (20-30 g body weight) (n = 6) were fed a standard laboratory diet and given Carboxymethylcellulose sodium (CMC), 150 mg/kg GMCT (GMCT-150), 300 mg/kg GMCT (GMCT-300) or 50 mg/kg Oxymetholone (OXY) via oral gavage for 21 days. On day 22, the animals' physical performance and muscle strength were assessed in a forced swimming test (FST) and forelimb grip strength experiment, respectively. In the human trial, thirty-eight resistance-trained young adults (mean age 26.32 ± 4.39 years, body weight 67.79 ± 12.84 kg, BMI 22.92 ± 3.54 kg/m) completed the trial. The participants received either GMCT (n = 19; 800 mg daily) or matched placebo (n = 19) for 42 days. As primary variables, 1-RM bench press, 1-RM leg press, and leg extension repetitions were measured at baseline and on days 14, 28 and 42 of the intervention. Anthropometric parameters and serum markers such as free testosterone, insulin-like growth factor 1 (IGF-1), insulin and lactate were also measured before and after the intervention.
RESULTS
GMCT-300 mice showed significant improvement in swimming time (GMCT: 395.3 ± 81.70 s vs. CMC: 271.6 ± 56.86 s; p = 0.0166), distance (GMCT: 341.22 ± 65.88 m vs. CMC: 260.84 ± 49.15 m; p = 0.0461) and grip strength (GMCT: 43.92 ± 6.97 N vs. CMC: 35.0 ± 6.92 N; p = 0.0490), compared with the CMC group. At the end of the 42-day human trial, the per protocol analyses reveal that mean changes from baseline 1-RM bench press (GMCT: 23.47 ± 10.07 kg vs. PL: 3.42 ± 2.06 kg; p < 0.0001), leg press (GMCT: 29.32 ± 16.17 kg vs. PL: 5.21 ± 1.72 kg; p < 0.0001), number of leg extension repetitions (GMCT: 6.58 ± 2.57 vs. PL: 2.05 ± 1.22; p < 0.0001) in GMCT group were significantly improved, compared with placebo. Intergroup difference analyses show that the changes from baseline left arm (GMCT: 1.09 ± 0.36 cm vs. PL: 0.68 ± 0.42 cm; p = 0.0023), right arm (GMCT: 1.50 ± 0.44 cm vs. PL: 1.11 ± 0.43 cm; p = 0.0088) circumference and lean mass (GMCT: 2.29 ± 2.09 kg vs. PL: 0.52 ± 2.58 kg; p = 0.0404) in GMCT group were also significantly improved, compared with placebo. In comparison to placebo, GMCT supplementation did not improve free testosterone, IGF-1, insulin or lactate levels. Parameters of clinical biochemistry, hematology, urine and vital signs of the participants were within the normal range.
CONCLUSION
GMCT supplementation is effective in increasing muscle strength, muscle size and, total lean mass, as well as endurance performance.
TRIAL REGISTRATION
Clinical Trial Registry of India (CTRI/2015/01/005374), Registered on Jan 07, 2015; CTRI Website URL - http://ctri.nic.in.
Topics: Adult; Animals; Cinnamomum; Double-Blind Method; Fruit; Garcinia mangostana; Humans; Insulin; Insulin-Like Growth Factor I; Lactic Acid; Male; Mice; Muscle Strength; Physical Endurance; Plant Extracts; Plant Leaves; Resistance Training; Testosterone; Young Adult
PubMed: 30348185
DOI: 10.1186/s12970-018-0257-4 -
Hormones and Behavior Dec 1997Anabolic-androgenic steroid (AAS) compounds are synthetic androgens taken by athletes to increase physical strength and endurance. Recent studies in our laboratory have...
Anabolic-androgenic steroid (AAS) compounds are synthetic androgens taken by athletes to increase physical strength and endurance. Recent studies in our laboratory have demonstrated that AAS administration disrupts the estrous cycle of Long-Evans rats. The present experiments examined the effects of six commonly abused AAS compounds on sexual receptivity in ovariectomized rats. Adult female Long-Evans rats received estradiol benzoate (EB; 2.0 micrograms/day s.c.) for 6 consecutive days followed by 15 days of EB concurrent with daily s.c. injections of 7.5 mg/kg of one of the following AAS compounds: 17 alpha-methyltestosterone, methandrostenolone, nandrolone decanoate, stanozolol, oxymetholone, testosterone cypionate, or the oil vehicle. On Day 15, all female rats received progesterone (1.0 mg/rat) 4 h before testing. Tests for sexual receptivity were conducted on Days 3, 6, 14, and 15 of AAS treatment. Although the time course of AAS effects on sexual receptivity varied, some overall effects were clear. For example, 17 alpha-methyltestosterone, methandrostenolone, nandrolone decanoate, and stanozolol interfered with the display of sexual receptivity on Day 14, whereas oxymetholone and testosterone cypionate had no effect. Rats in all groups displayed high levels of sexual receptivity after receiving progesterone on Day 15. Our results show that AAS compounds vary in their degree of inhibition of female sexual behavior in ovariectomized rats.
Topics: Anabolic Agents; Androgens; Animals; Estradiol; Female; Methandrostenolone; Methyltestosterone; Nandrolone; Ovariectomy; Oxymetholone; Posture; Rats; Sexual Behavior, Animal; Testosterone
PubMed: 9454671
DOI: 10.1006/hbeh.1997.1422 -
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 -
Blood Jul 1968
Topics: Adolescent; Anemia, Aplastic; Blood Cell Count; Child; Female; Hemoglobinometry; Humans; Male; Oxymetholone; Reticulocytes; Virilism
PubMed: 5658392
DOI: No ID Found -
British Journal of Cancer Oct 1972The effect of the anabolic steroids nandrolone decanoate and oxymetholone on the peripheral blood haemoglobin, total leucocyte and platelet counts was studied in a... (Clinical Trial)
Clinical Trial
The effect of the anabolic steroids nandrolone decanoate and oxymetholone on the peripheral blood haemoglobin, total leucocyte and platelet counts was studied in a controlled trial in which patients received standardized chemotherapy for one form of malignant disease. The results indicate that these agents have no protective effect on bone marrow suppression during cytotoxic chemotherapy. It was observed that the time interval between the initial nadir total leucocyte count and the return to pre-treatment values in those patients receiving the anabolic steroids was significantly shorter than in the control group.
Topics: Adolescent; Adult; Anabolic Agents; Blood Cell Count; Blood Platelets; Bone Marrow; Choriocarcinoma; Clinical Trials as Topic; Female; Hematocrit; Hematopoiesis; Hemoglobins; Humans; Hydatidiform Mole, Invasive; Leukocyte Count; Methotrexate; Nandrolone; Oxymetholone; Pregnancy; Time Factors
PubMed: 4343678
DOI: 10.1038/bjc.1972.52 -
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 -
Blood Jun 1975Seven patients with sickle cell anemia were treated with oxymetholone for at least 2 mo. Markedly increased basal rates of hemolysis and erythropoiesis were confirmed....
Seven patients with sickle cell anemia were treated with oxymetholone for at least 2 mo. Markedly increased basal rates of hemolysis and erythropoiesis were confirmed. The urinary erythropoietin excretion was either normal or lower than expected for the red cell mass, and an expanded blood volume was due primarily to an increased plasma volume. After androgen therapy, six patients demonstrated more than a fivefold increase in urinary erythropoietin, with an increase in red cell mass ranging from 17%-75% above the control value. All showed a decline in serum iron level to the 25-75 mug/100 ml range within 4 wk after the start of therapy. Less marked changes followed lower oxymetholone doses. Reversible hepatic toxicity, with a serum bilirubin concentration exceeding 50 mg/100 ml, occurred in one patient. Androgenic hormone therapy may be useful for selected adult patients with sickle cell disease when severe anemia contributes to disease morbidity.
Topics: Adolescent; Adult; Androgens; Anemia, Sickle Cell; Bilirubin; Blood Volume; Cell Survival; Chromium Radioisotopes; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Hematocrit; Hemolysis; Humans; Iron; Iron Radioisotopes; Liver; Liver Function Tests; Male; Middle Aged; Oxymetholone
PubMed: 1125426
DOI: No ID Found -
British Journal of Haematology Oct 2019
Topics: Adult; Aged; Aged, 80 and over; Androgens; Danazol; Female; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Oxymetholone; Retrospective Studies; Thrombocytopenia; Treatment Outcome; Young Adult
PubMed: 31368111
DOI: 10.1111/bjh.16121