RESUMO
A reliable method using a QuEChERS approach and liquid chromatography coupled to Q-Orbitrap mass spectrometry was optimized and validated for the quantification of 20 growth promoters in bovine serum. The recoveries ranged from 91.4-114.1%, relative standard deviations varied between 0.3-4.0%, and CCα values were between 0.023-0.350 µg L-1. The developed method was applied in an in vivo study using steers, which were intramuscularly treated with commercial injections containing stanozolol. A rapid metabolization was observed, with a detection window ranging from 3 to 10 days. The stability of incurred stanozolol was confirmed after 240 days at -20 °C and also after 5 freeze-thaw cycles. To the best of our knowledge, this is the first work in which an in vivo study was performed to support the monitoring of stanozolol in bovine serum. In addition, the use of Q-Orbitrap high-resolution mass spectrometry allows for retrospective analysis from a surveillance perspective.
Assuntos
Estanozolol , Cromatografia Líquida de Alta Pressão/métodos , Estudos Retrospectivos , Espectrometria de Massas/métodos , Cromatografia LíquidaRESUMO
An in vivo study was performed in order to evaluate the depletion time of stanozolol and its main metabolites using naturally incurred urine sample collected after the administration of intramuscular injections in 12 steers. A stability study was also carried out to investigate the influence of the storage period and the freeze-thaw cycles. A fast parent drug metabolization was observed, because within 6 h after drug administration, the signal of the metabolite 16ß-hydroxystanozolol was predominant. After the second drug administration, a detection window of 17 days was obtained. The stability was studied using ANOVA, in which a storage condition of -20 °C proved stable during 240 days, which was also confirmed after 5 freeze-thaw cycles.
Assuntos
Estanozolol , Animais , Bovinos , Cromatografia Líquida de Alta Pressão , Injeções Intramusculares , Estanozolol/urinaRESUMO
Los antibióticos y analgésicos han sido descritos frecuentemente como las principales causas de toxicidad hepática. Los esteroides anabólicos se han relacionado también con alteraciones en sistemas como el cardiovascular o el hepático; en este último causan colestasis, carcinoma hepatocelular, hiperplasia regenerativa nodular y sangrado de varices, secundario a hipertensión portal. Es importante entonces considerar los esteroides anabólicos como factores de riesgo para hepatotoxicidad. Se presenta el primer caso en Colombia y uno de los pocos en Latinoamérica, de colestasis asociada únicamente al uso de estanozolol. Se trata de un paciente de 21 años, en tratamiento con el medicamento para incrementar la masa muscular, que presentó compromiso hepático de tipo colestásico. Se descartaron otras posibles causas de ictericia, mediante la escala CIOMS/RUCAM se llegó a establecer causalidad entre el consumo de estanozolol y la colestasis. El objetivo de este reporte es hacer una descripción no reportada en la literatura colombiana y poco común en la literatura mundial.
Antibiotics and pain relievers have been frequently described as the main causes of liver toxicity. Anabolic steroids have also been linked to alterations in systems such as cardio-vascular or liver. In the latter, they seem to cause cholestasis, hepatocellular carcinoma, nodular regenerative hyperplasia and variceal bleeding secondary to portal hypertension. It is important to consider them as factors associated with hepatotoxicity. The first case in Colombia and one of the few in Latin America of cholestasis associated only to the use of Stanozolol is presented in a 21-year-old patient under treatment with the drug to increase muscle mass. The patient presented with cholestatic liver involvement. Other possible causes of jaundice were ruled out. From the CIOMS / RUCAM scale, causality was established between the consumption of Stanozolol and cholestasis. The objective of this case is to report a case not found in Colombian literature and little reported in world literature.
Antibióticos e analgésicos têm sido frequentemente descritos como as principais causas de toxicidade hepática. Os esteroides anabolizantes também têm sido relacionados a alterações em sistemas como cardiovasculares ou hepáticos; neste último, causam colestase, carcinoma hepatocelular, hiperplasia nodular regenerativa e sangramento varicoso, secundário à hipertensão portal. Portanto, é importante considerar os este-roides anabolizantes como fatores de risco para hepatotoxicidade. O primeiro caso é apresentado na Colômbia e um dos poucos na América Latina, de colestase associada apenas ao uso de estanozolol. Paciente de 21 anos, em tratamento com fármaco para aumento de massa muscular, apresentou acometimento hepático colestático. Outras possíveis causas de icterícia foram descartadas, a escala CIOMS / RUCAM estabeleceu causalidade entre o consumo de estanozolol e colestase. O objetivo deste relatório é fazer uma descrição não relatada na literatura colombiana e rara na literatura mundial
Assuntos
Humanos , Estanozolol , Anabolizantes , Colestase , Congêneres da Testosterona , Icterícia , FígadoRESUMO
Abstract Anabolic substances have been increasingly used by bodybuilders and athletes with the goal of improving performance and aesthetics. However, this practice has caused some concern to physicians and researchers because of unknowledge of consequences that the indiscriminate and illicit use of these substances can cause. Thus, this study analyzed the effects of two commercially available anabolic steroids (AS), Winstrol Depot® (Stanozolol) and Deposteron® (Testosterone Cypionate), in the neuronal density of limbic, motor and sensory regions on the cerebral cortex and in CA1, CA2, CA3 regions of the hippocampus. A total of 60 Swiss mice were used (30 males and 30 females), separated into three groups: control and two experimental groups, which received the AAS. From each brain, homotypic and semi-serial samples were taken in frontal sections from areas established for the study. The results showed that females treated with testosterone cypionate presented a reduction in all regions tested and the ones treated with Stanozolol showed a decrease in some hippocampal areas. Regarding male animals, stanozolol led to a decrease in neuron number in one hippocampal region. These data allow us to conclude that supra-physiological doses of steroids used in this study, can cause considerable damage to nervous tissue with ultrastructural and consequently behavioral impairment. These changes could interfere with the loss of physical yield and performance of athletes and non-athletes and may cause irreparable damage to individuals making irresponsible use of anabolic steroids.
Resumo As substancias anabólicas tem sido cada vez mais utilizadas por fisiculturistas e atletas com o objetivo de melhorar o desempenho e a estética. No entanto, essa prática tem causado algumas preocupações aos médicos e pesquisadores, devido ao desconhecimento das consequencias que o uso indiscriminado e ilícito dessas substâncias podem causar. Diante disso, este estudo analisou os efeitos de dois esteroides anabolizantes (EA) comercialmente disponíveis, Winstrol Depot® (Stanozolol) e Deposteron® (cipionato de testosterona), na densidade neuronal das regiões corticais límbica, motora e sensitive bem como das áreas CA1, CA2, CA3 do hipocampo. Foram utilizados 60 camundongos Swiss (30 machos e 30 fêmeas), separados em três grupos: controle e dois grupos experimentais, que receberam o EA. De cada cérebro, foram coletadas amostras homotípicas e semi-seriadas em cortes frontais das áreas estabelecidas para o estudo. Os resultados mostraram que as fêmeas tratadas com cipionato de testosterona apresentaram uma redução em todas as regiões analisadas já as fêmeas tratadas com Stanozolol mostraram uma diminuição em algumas áreas do hipocampo. Em relação aos animais machos, o stanozolol levou a uma diminuição na densidade neuronal em uma região do hipocampo. Estes dados nos permitem concluir que doses supra fisiológicas de esteroides utilizadas neste estudo podem causar danos consideráveis ao tecido nervoso com comprometimento ultraestrutural e consequentemente comportamental. Essas alterações podem interferir na perda de rendimento físico e no desempenho de atletas e não atletas e podem causar danos irreparáveis a indivíduos que fazem uso irresponsável destes EA.
Assuntos
Animais , Masculino , Feminino , Coelhos , Anabolizantes/efeitos adversos , Estanozolol/efeitos adversos , Congêneres da Testosterona , Hipocampo , NeurôniosRESUMO
Anabolic substances have been increasingly used by bodybuilders and athletes with the goal of improving performance and aesthetics. However, this practice has caused some concern to physicians and researchers because of unknowledge of consequences that the indiscriminate and illicit use of these substances can cause. Thus, this study analyzed the effects of two commercially available anabolic steroids (AS), Winstrol Depot® (Stanozolol) and Deposteron® (Testosterone Cypionate), in the neuronal density of limbic, motor and sensory regions on the cerebral cortex and in CA1, CA2, CA3 regions of the hippocampus. A total of 60 Swiss mice were used (30 males and 30 females), separated into three groups: control and two experimental groups, which received the AAS. From each brain, homotypic and semi-serial samples were taken in frontal sections from areas established for the study. The results showed that females treated with testosterone cypionate presented a reduction in all regions tested and the ones treated with Stanozolol showed a decrease in some hippocampal areas. Regarding male animals, stanozolol led to a decrease in neuron number in one hippocampal region. These data allow us to conclude that supra-physiological doses of steroids used in this study, can cause considerable damage to nervous tissue with ultrastructural and consequently behavioral impairment. These changes could interfere with the loss of physical yield and performance of athletes and non-athletes and may cause irreparable damage to individuals making irresponsible use of anabolic steroids.
Assuntos
Anabolizantes , Anabolizantes/efeitos adversos , Animais , Feminino , Hipocampo , Masculino , Camundongos , Neurônios , Estanozolol/efeitos adversos , Congêneres da TestosteronaRESUMO
A busca pelo corpo perfeito pode gerar graves consequências para a população que faz uso indiscriminado de substâncias visando a resultados rápidos. O caso relatado se refere a um pa- ciente de 21 anos, do sexo masculino, na cidade de São Paulo (SP), que apresentou quadro de síndrome colestática 15 dias após uso do anabolizante estanazolol para fins estéticos na ativi- dade física, evoluindo com hepatite medicamentosa grave, com aumento de transaminases, hiperrubilinemia às custas de bilirrubina direta e fatores de coagulação, sem resposta satis- fatória ao tratamento de suporte convencional, com melhora significativa após introdução de corticoterapia.
Searching for the perfect body image can cause severe conse- quences to the population using substances indiscriminately to reach results fast. The case reported refers to a male patient, 21 years old, from the city of São Paulo (SP), who developed choles- tatic syndrome 15 days after the use of the steroid Stanazol for aesthetic purposes during physical activity, progressing with se- vere drug-induced hepatitis, transaminases, bilirubin, and coagu- lation factors increase with no satisfactory response to the con- ventional support treatment, and significant improvement after the introduction of corticotherapy.
Assuntos
Humanos , Masculino , Adulto , Adulto Jovem , Estanozolol/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Glucocorticoides/uso terapêutico , Anabolizantes/toxicidade , Ácido Ursodesoxicólico/administração & dosagem , Bilirrubina/sangue , Biópsia , Colagogos e Coleréticos/uso terapêutico , Prednisona/administração & dosagem , Colestase/diagnóstico , Colestase/patologia , Colesterol/sangue , Resina de Colestiramina/administração & dosagem , Doença Catastrófica , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/patologia , Transaminases/sangue , Hidroxizina/administração & dosagem , Fígado/patologia , Anticolesterolemiantes/uso terapêutico , Antipruriginosos/uso terapêuticoRESUMO
No presente estudo, foram analisados os efeitos do estanozolol, associado ou não à atividade física, sobre o hemograma, o peso ponderal, a ingestão líquida e sólida, a urinálise, a expressão do VEGF-A renal e o glicogênio hepático, além da histopatologia hepática e renal em ratos Wistar. Foram utilizados 32 ratos Wistar, machos, jovens, separados em quatro grupos: GC (grupo controle); GCE (grupo controle-exercício); GT (grupo tratamento-esteroide); GTE (grupo tratamento-esteroide-exercício). Os animais dos grupos GT e GTE (n=16) foram submetidos a injeções subcutâneas, cinco dias/semana, durante 30 dias, na concentração de 5mg/kg de estanozolol diluído em 1mL de óleo de gergelim, utilizado como veículo. A natação foi definida como exercício físico. Houve aumento no peso dos animais submetidos ao estanozolol e ao exercício a partir da terceira semana de uso e aumento da excreção urinária a partir da quinta semana; os demais parâmetros da urinálise foram semelhantes entre os grupos. O uso de estanozolol associado ou não à atividade física promoveu redução da expressão do VEGF-A nos rins e do glicogênio hepático, além de alterações histopatológicas nesses órgãos. Quanto à hematologia, houve uma diminuição dos leucócitos no GTE em relação aos grupos GT e GCE. Quanto aos linfócitos, houve um aumento no GT e uma diminuição no GTE, e, em relação ao número de plaquetas, houve diminuição no GTE quando comparado ao GT e ao GCE Assim, conclui-se que estanozolol na dose de 5,0mg/kg causa alterações renais e hepáticas em ratos Wistar, podendo levar à falência dos rins e do fígado.(AU)
The goal of this study was to determine the effect of stanozolol (ST) on kidney and liver of Wistar rats. Thirty-two male animals were divided into the following four groups: control group (CG); Control group-exercise (GCE); Group-steroid treatment (GT); Group treatment-steroid-exercise (GTE). Swimming was defined as exercise. The animals GT and GTE was submitted to subcutaneous injections, five days/week for 30 days, at a concentration of 5mg/kg ST diluted in 1mL/kg of sesame oil. The results showed an increase in weight gain in all animals submitted to ST and exercise from the 3rd week of use and increase in urinary excretion from the 5th week and the other urinalysis parameters were similar. The ST associated or not with physical activity reduced VEGF-A expression in the kidneys and hepatic glycogen, as well as histopathological changes in these organs. Regarding hematology, there was a decrease in leukocytes in the GTE. As for lymphocytes there was an increase in GT and a decrease in GTE, and in relation to the number of platelets, there was a decrease in GTE. In conclusion, the administration of stanozolol at 5.0mg/kg caused a structural change of kidney and liver in treated animals.(AU)
Assuntos
Animais , Ratos , Estanozolol/administração & dosagem , Natação , Rim/anatomia & histologia , Fígado/efeitos dos fármacos , Ratos Wistar/fisiologia , Anabolizantes/administração & dosagem , Testes de Função Renal/veterináriaRESUMO
No presente estudo, foram analisados os efeitos do estanozolol, associado ou não à atividade física, sobre o hemograma, o peso ponderal, a ingestão líquida e sólida, a urinálise, a expressão do VEGF-A renal e o glicogênio hepático, além da histopatologia hepática e renal em ratos Wistar. Foram utilizados 32 ratos Wistar, machos, jovens, separados em quatro grupos: GC (grupo controle); GCE (grupo controle-exercício); GT (grupo tratamento-esteroide); GTE (grupo tratamento-esteroide-exercício). Os animais dos grupos GT e GTE (n=16) foram submetidos a injeções subcutâneas, cinco dias/semana, durante 30 dias, na concentração de 5mg/kg de estanozolol diluído em 1mL de óleo de gergelim, utilizado como veículo. A natação foi definida como exercício físico. Houve aumento no peso dos animais submetidos ao estanozolol e ao exercício a partir da terceira semana de uso e aumento da excreção urinária a partir da quinta semana; os demais parâmetros da urinálise foram semelhantes entre os grupos. O uso de estanozolol associado ou não à atividade física promoveu redução da expressão do VEGF-A nos rins e do glicogênio hepático, além de alterações histopatológicas nesses órgãos. Quanto à hematologia, houve uma diminuição dos leucócitos no GTE em relação aos grupos GT e GCE. Quanto aos linfócitos, houve um aumento no GT e uma diminuição no GTE, e, em relação ao número de plaquetas, houve diminuição no GTE quando comparado ao GT e ao GCE Assim, conclui-se que estanozolol na dose de 5,0mg/kg causa alterações renais e hepáticas em ratos Wistar, podendo levar à falência dos rins e do fígado.(AU)
The goal of this study was to determine the effect of stanozolol (ST) on kidney and liver of Wistar rats. Thirty-two male animals were divided into the following four groups: control group (CG); Control group-exercise (GCE); Group-steroid treatment (GT); Group treatment-steroid-exercise (GTE). Swimming was defined as exercise. The animals GT and GTE was submitted to subcutaneous injections, five days/week for 30 days, at a concentration of 5mg/kg ST diluted in 1mL/kg of sesame oil. The results showed an increase in weight gain in all animals submitted to ST and exercise from the 3rd week of use and increase in urinary excretion from the 5th week and the other urinalysis parameters were similar. The ST associated or not with physical activity reduced VEGF-A expression in the kidneys and hepatic glycogen, as well as histopathological changes in these organs. Regarding hematology, there was a decrease in leukocytes in the GTE. As for lymphocytes there was an increase in GT and a decrease in GTE, and in relation to the number of platelets, there was a decrease in GTE. In conclusion, the administration of stanozolol at 5.0mg/kg caused a structural change of kidney and liver in treated animals.(AU)
Assuntos
Animais , Ratos , Estanozolol/administração & dosagem , Natação , Rim/anatomia & histologia , Fígado/efeitos dos fármacos , Ratos Wistar/fisiologia , Anabolizantes/administração & dosagem , Testes de Função Renal/veterináriaRESUMO
Testosterone cypionate and Stanozolol are Anabolic-Androgenic Steroids (AAS) which are synthetic substances that possess functions similar to testosterone. The use of these substances has increased considerably among youngsters and sports practitioners aiming better performance of with aesthetic purposes. The major concern is the effects caused by the inappropriate use of the substances, such as hypertension, myocardial ischemia, and left ventricle hypertrophy. The objective of the present research was to measure the diameter of the left ventricle lumen and the thickness of the left ventricle myocardium in mice submitted to supraphysiological doses of AAS. A total of 30 female Swiss mice were used in the experiments. The animals received supraphysiological doses of the AAS for 30â¯days, and during the treatment period, they were put to swim in intercalated days. After treatment animals were euthanized and slides were made from the hearts for measurements. Results demonstrated that both AAS changed significantly the heart morphology: Testosterone cypionate led to an increase in the ventricular lumen and stanozolol increased left ventricle myocardium thickness. In conclusion, the use of AAS in supraphysiological doses can change the heart morphology and can lead to serious health consequences.
Assuntos
Coração/efeitos dos fármacos , Condicionamento Físico Animal , Estanozolol/farmacologia , Testosterona/análogos & derivados , Animais , Feminino , Coração/fisiologia , Camundongos , Testosterona/farmacologiaRESUMO
The aim of the study was to evaluate the effect of an anabolic steroid, stanozolol, in a model of atherosclerosis and to investigate the involvement of the modulation of the inflammatory cytokines and oxidative stress in vascular lipid deposition. Low-density lipid receptor-deficient (LDLr-/-) mice were fed a standard chow diet and were each week injected subcutaneously either saline (control C group) or 20 mg/kg stanozolol (S group). After 8 weeks, the levels of cholesterol, oxidized LDL (OxLDL) and cytokines were measured in plasma, lipid deposition in aorta was evaluated by en face analysis, and thiobarbituric acid-reactive substances and oxidation protein were determined in liver. The S group demonstrated increases in vascular lipid deposition, triglycerides and non-HDL cholesterol levels. Stanozolol increased tumour necrosis factor alpha (TNF-α) and decreased interleukin-10 as well as increased the TNF-α/IL-10 ratio. Furthermore, oxidative stress was observed in the S group, as indicated by an increase in the plasma OxLDL, as well as by lipid peroxidation and oxidation of proteins in the liver. Chronic treatment with stanozolol promoted lipid deposition in the LDLr-/- mice that could be attributed to a modification of the circulating cytokine levels and systemic oxidative stress. Our results suggest that the anabolic steroid stanozolol in the absence of functional LDL receptors by increasing systemic inflammation and oxidative stress may increase the risk of development and progression of atherosclerosis.
Assuntos
Aterosclerose/induzido quimicamente , Metabolismo dos Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estanozolol/toxicidade , Anabolizantes/toxicidade , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Aterosclerose/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Inflamação/induzido quimicamente , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Lipoproteínas LDL/metabolismo , Masculino , Camundongos , Camundongos Knockout , Oxirredução/efeitos dos fármacos , Receptores de LDL/genéticaRESUMO
A lipodermatoesclerose é uma paniculite que se caracteriza por endurecimento e hiperpigmentação da pele envolvendo as panturrilhas, com a aparência de "garrafa de champanhe invertida". Muitas abordagens terapêuticas têm sido recomendadas, mas o uso de oxandrolona para essa finalidade foi pouco estudado até o momento. Relatamos um caso de lipodermatoesclerose aguda em uma mulher de 61 anos, com história prévia de tratamento cirúrgico para insuficiência venosa de membros inferiores. A paciente apresentava edema e lesões dolorosas e eritematosas com infiltração difusa, que acometiam principalmente a face posterior da panturrilha esquerda. Foi tratada inicialmente com estanozolol e pentoxifilina, com boa resposta. Devido à indisponibilidade do estanozolol, iniciou-se o uso de oxandrolona. Esse tratamento foi bem tolerado, resultando em redução significativa do edema, do eritema e da infiltração presentes nos membros inferiores, além de alívio da dor. A oxandrolona pode representar uma opção útil e segura no tratamento da lipodermatoesclerose aguda
Lipodermatosclerosis is a panniculitis characterized by hardening and hyperpigmentation of the skin involving the calves with an "inverted champagne bottle" appearance. Many therapeutic approaches have been recommended, but the use of oxandrolone for this purpose has been studied very little to date. We report a case of acute lipodermatosclerosis in a 61-year-old woman with a previous history of surgical treatment for venous insufficiency of the lower limbs. The patient presented with edema and painful, erythematous lesions with diffuse infiltration, mainly affecting the posterior aspect of the left calf. She was initially treated with stanozolol and pentoxifylline, with good response. Due to unavailability of stanozolol, she was put on oxandrolone. This treatment was well tolerated, reduced the intensity of edema, erythema, and infiltration in the lower limbs, effectively leading to pain relief. Oxandrolone may be a useful and safe treatment for patients with acute lipodermatosclerosis
Assuntos
Oxandrolona/uso terapêutico , Paniculite , Pentoxifilina , Estanozolol , Insuficiência Venosa/terapia , Extremidade InferiorRESUMO
Abstract Stanozolol (ST) is a synthetic androgen with high anabolic potential. Although it is known that androgens play a positive role in bone metabolism, ST action on bone cells has not been sufficiently tested to support its clinical use for bone augmentation procedures. Objective: This study aimed to assess the effects of ST on osteogenic activity and gene expression in SaOS-2 cells. Material and Methods: SaOS-2 deposition of mineralizing matrix in response to increasing doses of ST (0-1000 nM) was evaluated through Alizarin Red S and Calcein Green staining techniques at 6, 12 and 24 days. Gene expression of runt-related transcription factor 2 (RUNX2), vitamin D receptor (VDR), osteopontin (SPP1) and osteonectin (ON) was analyzed by RT-PCR. Results: ST significantly influenced SaOS-2 osteogenic activity: stainings showed the presence of rounded calcified nodules, which increased both in number and in size over time and depending on ST dose. RT-PCR highlighted ST modulation of genes related to osteogenic differentiation. Conclusions: This study provided encouraging results, showing ST promoted the osteogenic commitment of SaOS-2 cells. Further studies are required to validate these data in primary osteoblasts and to investigate ST molecular pathway of action.
Assuntos
Humanos , Osteogênese/efeitos dos fármacos , Estanozolol/farmacologia , Expressão Gênica/efeitos dos fármacos , Anabolizantes/farmacologia , Osteoblastos/efeitos dos fármacos , Fatores de Tempo , Calcificação Fisiológica/efeitos dos fármacos , Modelos Lineares , Osteonectina/análise , Osteonectina/efeitos dos fármacos , Reprodutibilidade dos Testes , Análise de Variância , Receptores de Calcitriol/análise , Receptores de Calcitriol/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/análise , Subunidade alfa 1 de Fator de Ligação ao Core/efeitos dos fármacos , Osteopontina/análise , Osteopontina/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Stanozolol (ST) is a synthetic androgen with high anabolic potential. Although it is known that androgens play a positive role in bone metabolism, ST action on bone cells has not been sufficiently tested to support its clinical use for bone augmentation procedures. OBJECTIVE: This study aimed to assess the effects of ST on osteogenic activity and gene expression in SaOS-2 cells. MATERIAL AND METHODS: SaOS-2 deposition of mineralizing matrix in response to increasing doses of ST (0-1000 nM) was evaluated through Alizarin Red S and Calcein Green staining techniques at 6, 12 and 24 days. Gene expression of runt-related transcription factor 2 (RUNX2), vitamin D receptor (VDR), osteopontin (SPP1) and osteonectin (ON) was analyzed by RT-PCR. RESULTS: ST significantly influenced SaOS-2 osteogenic activity: stainings showed the presence of rounded calcified nodules, which increased both in number and in size over time and depending on ST dose. RT-PCR highlighted ST modulation of genes related to osteogenic differentiation. CONCLUSIONS: This study provided encouraging results, showing ST promoted the osteogenic commitment of SaOS-2 cells. Further studies are required to validate these data in primary osteoblasts and to investigate ST molecular pathway of action.
Assuntos
Anabolizantes/farmacologia , Expressão Gênica/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Estanozolol/farmacologia , Análise de Variância , Calcificação Fisiológica/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/análise , Subunidade alfa 1 de Fator de Ligação ao Core/efeitos dos fármacos , Humanos , Modelos Lineares , Osteoblastos/efeitos dos fármacos , Osteonectina/análise , Osteonectina/efeitos dos fármacos , Osteopontina/análise , Osteopontina/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Calcitriol/análise , Receptores de Calcitriol/efeitos dos fármacos , Reprodutibilidade dos Testes , Fatores de TempoRESUMO
We have studied the Fourier Transform Infrared (FT-IR) and the Fourier transform Raman (FT-Raman) spectra of stanozolol and oxandrolone, and we have performed quantum chemical calculations based on the density functional theory (DFT) with a B3LYP/6-31G (d, p) level of theory. The FT-IR and FT-Raman spectra were collected in a solid phase. The consistency between the calculated and experimental FT-IR and FT-Raman data indicates that the B3LYP/6-31G (d, p) can generate reliable geometry and related properties of the title compounds. Selected experimental bands were assigned and characterized on the basis of the scaled theoretical wavenumbers by their total energy distribution. The good agreement between the experimental and theoretical spectra allowed positive assignment of the observed vibrational absorption bands. Finally, the calculation results were applied to simulate the Raman and IR spectra of the title compounds, which show agreement with the observed spectra.
Assuntos
Anabolizantes/análise , Oxandrolona/análise , Teoria Quântica , Estanozolol/análise , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral RamanRESUMO
One of the greatest challenges in anti-doping science is the large number of substances available and the difficulty in finding the best analytical targets to detect their misuse. Therefore, metabolism studies involving prohibited substances are fundamental. However, metabolism studies in humans could face an important ethical bottleneck, especially for non-approved substances. An emerging model for metabolism assessment is the zebrafish, due to its genetic similarities with humans. In the present study, the ability of adult zebrafish to produce metabolites of sibutramine and stanozolol, substances with a well-known metabolism that are widely used as doping agents in sports, was evaluated. They represent 2 of the most abused classes of doping agents, namely, stimulants and anabolic steroids. These are classes that have been receiving attention because of the upsurge of synthetic analogues, for which the side effects in humans have not been assessed. The samples collected from the zebrafish tank water were hydrolysed, extracted by solid-phase extraction, and analysed by liquid chromatography with high resolution mass spectrometry (LC-HRMS). Adult zebrafish could produce several sibutramine and stanozolol metabolites, including demethylated, hydroxylated, dehydroxylated, and reduced derivatives, all of which have already been detected in human urine. This study demonstrates that adult zebrafish can absorb, oxidise, and excrete several metabolites in a manner similar to humans. Therefore, adult zebrafish seem to be a very promising tool to study human-like metabolism when aiming to find analytical targets for doping control. Copyright © 2017 John Wiley & Sons, Ltd.
Assuntos
Dopagem Esportivo , Estanozolol/urina , Peixe-Zebra , Adulto , Animais , Cromatografia Líquida , Humanos , Hidroxilação , Extração em Fase Sólida , Estanozolol/química , Espectrometria de Massas em TandemRESUMO
The aim of this study was to assess if the dose and exposure duration of the anabolic androgenic steroids (AAS) boldenone (BOL) and stanazolol (ST) affected memory, anxiety, and social interaction, as well as acetylcholinesterase (AChE) activity and oxidative stress in the cerebral cortex (CC) and hippocampus (HC). Male Wistar rats (90 animals) were randomly assigned to three treatment protocols: (I) 5 mg/kg BOL or ST, once a week for 4 weeks; (II) 2.5 mg/kg BOL or ST, once a week for 8 weeks; and (III) 1.25 mg/kg BOL or ST, once a week for 12 weeks. Each treatment protocol included a control group that received an olive oil injection (vehicle control) and AAS were administered intramuscularly (a total volume of 0.2 ml) once a week in all three treatment protocols. In the BOL and ST groups, a higher anxiety level was observed only for Protocol I. BOL and ST significantly affected social interaction in all protocols. Memory deficits and increased AChE activity in the CC and HC were found in the BOL groups treated according to Protocol III only. In addition, BOL and ST significantly increased oxidative stress in both the CC and HC in the groups treated according to Protocol I and III. In conclusion, our findings show that the impact of BOL and ST on memory, anxiety, and social interaction depends on the dose and exposure duration of these AAS.
Assuntos
Acetilcolinesterase/metabolismo , Anabolizantes/farmacologia , Androgênios/farmacologia , Comportamento Animal/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Agressão/efeitos dos fármacos , Anabolizantes/administração & dosagem , Androgênios/administração & dosagem , Animais , Relação Dose-Resposta a Droga , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Masculino , Ratos Wistar , Estanozolol/administração & dosagem , Estanozolol/farmacologia , Territorialidade , Testosterona/administração & dosagem , Testosterona/análogos & derivados , Testosterona/farmacologiaRESUMO
O objetivo deste trabalho é agrupar e revisar os dados literários a respeito do tratamento intra-articular de estanozolol micronizado em equinos com osteoartrite, visando uma análise da sua aplicabilidade na prática da medicina equina. Estanozolol é um derivado sintético da testosterona. Na terapêutica humana atualmente ele é usado em diversas condições clínicas, como para estimular a eritropoiese em algumas formas de anemia. Estudos sugerem que essa droga possui propriedades anti-inflamatórias, reduz a apoptose em condrócitos equínos pela depleção da produção de óxido nítrico e estimulando o fator de crescimento semelhante a insulina, estimula a proliferação osteoblástica, bem como a produção de matriz óssea e síntese de fatores de crescimento, além de função antagonista ao paratormônio e IL-1,impedindo a degeneração do componente mineral. Diversos experimentos em equinos têm sido realizados visando avaliar o comportamento do estanozolol micronizado no meio articular e sua influência sobre a doença articular degenerativa. Ao fim dessa revisão de literatura pode-se concluir que o estanozolol micronizado quando usado repetidamente na dose de 5 mg intra-articular, em uma articulação com sinais de osteoartrite aguda ou crônica, conseguiu diminuir o grau de claudicação dos animais, assim como reduzir alterações morfológicas e melhorar o líquido sinovial em equinos atletas, justificando seu uso como droga antiartrítica.(AU)
The objective of this study is to gather and review the literary data about the intra-articular treatment of Stanozolol micronized in horses with osteoarthritis, aiming to analyze their applicability in the practice of equine medicine. Stanozolol is a synthetic derivative of testosterone. In human therapy it is currently used in several clinical conditions, such as for stimulating erythropoiesis in some forms of anemia. Studies suggest that this drug has anti-inflammatory properties, reduces apoptosis in chondrocytes horses by depletion of nitric oxide production and stimulating growth factor like insulin, stimulates osteoblast proliferation and the production of bone matrix and synthesis factors growth, and function antagonistic to PTH, and IL-1by preventing the degeneration of the mineral component. Several experiments in horses have been conducted to evaluate the micronized Stanozolol behavior in middle joint and its influence on degenerative joint disease. At the end of this literature review it can be concluded that the micronised stanozolol when used repeatedly at dose intraarticular 5mg in a joint with acute signs of osteoarthritis or chronic, managed to decrease the level of animal claudication, as well as reducing morphological changes and improve synovial fluid in equine athletes, justifying its use as antiarthritic drug.(AU)
El objetivo de este estudio es reunir y revisar los datos literarios sobre el tratamiento intra-articular de estanozolol micronizado en caballos con osteoartritis, con el objetivo de analizar su aplicabilidad en la práctica de la medicina equina. El estanozolol es un derivado sintético de la testosterona. En la terapia humana se utiliza actualmente en varias condiciones clínicas, como para estimular la eritropoyesis en algunas formas de anemia. Los estudios sugieren que este fármaco tiene propiedades antiinflamatorias, reduce la apoptosis en los caballos condrocitos por el agotamiento de la producción de óxido nítrico y el factor de crecimiento estimulante como la insulina, estimula la proliferación de osteoblastos y la producción de crecimiento de la matriz ósea y los factores de síntesis. IL-1previniendo la degeneración del componente mineral. Se han realizado varios experimentos en caballos para evaluar el comportamiento micronizado del estanozolol en la articulación media y su influencia en la enfermedad degenerativa de las articulaciones. Al final de esta revisión de la literatura se puede concluir que el estanozolol micronizado cuando se utiliza repetidamente a dosis intraarticular 5 mg en una articulación con signos agudos de osteoartritis o crónica, logró diminuir el nivel de claudicación animal, así como reducir los cambios morfológicos y mejorar Sinovial en atletas equinos, justificando su uso como fármaco antiartrítico.(AU)
Assuntos
Animais , Estanozolol/uso terapêutico , Osteoartrite/terapia , Osteoartrite/veterinária , Cavalos , Anti-InflamatóriosRESUMO
O objetivo deste trabalho é agrupar e revisar os dados literários a respeito do tratamento intra-articular de estanozolol micronizado em equinos com osteoartrite, visando uma análise da sua aplicabilidade na prática da medicina equina. Estanozolol é um derivado sintético da testosterona. Na terapêutica humana atualmente ele é usado em diversas condições clínicas, como para estimular a eritropoiese em algumas formas de anemia. Estudos sugerem que essa droga possui propriedades anti-inflamatórias, reduz a apoptose em condrócitos equínos pela depleção da produção de óxido nítrico e estimulando o fator de crescimento semelhante a insulina, estimula a proliferação osteoblástica, bem como a produção de matriz óssea e síntese de fatores de crescimento, além de função antagonista ao paratormônio e IL-1,impedindo a degeneração do componente mineral. Diversos experimentos em equinos têm sido realizados visando avaliar o comportamento do estanozolol micronizado no meio articular e sua influência sobre a doença articular degenerativa. Ao fim dessa revisão de literatura pode-se concluir que o estanozolol micronizado quando usado repetidamente na dose de 5 mg intra-articular, em uma articulação com sinais de osteoartrite aguda ou crônica, conseguiu diminuir o grau de claudicação dos animais, assim como reduzir alterações morfológicas e melhorar o líquido sinovial em equinos atletas, justificando seu uso como droga antiartrítica.
The objective of this study is to gather and review the literary data about the intra-articular treatment of Stanozolol micronized in horses with osteoarthritis, aiming to analyze their applicability in the practice of equine medicine. Stanozolol is a synthetic derivative of testosterone. In human therapy it is currently used in several clinical conditions, such as for stimulating erythropoiesis in some forms of anemia. Studies suggest that this drug has anti-inflammatory properties, reduces apoptosis in chondrocytes horses by depletion of nitric oxide production and stimulating growth factor like insulin, stimulates osteoblast proliferation and the production of bone matrix and synthesis factors growth, and function antagonistic to PTH, and IL-1by preventing the degeneration of the mineral component. Several experiments in horses have been conducted to evaluate the micronized Stanozolol behavior in middle joint and its influence on degenerative joint disease. At the end of this literature review it can be concluded that the micronised stanozolol when used repeatedly at dose intraarticular 5mg in a joint with acute signs of osteoarthritis or chronic, managed to decrease the level of animal claudication, as well as reducing morphological changes and improve synovial fluid in equine athletes, justifying its use as antiarthritic drug.
El objetivo de este estudio es reunir y revisar los datos literarios sobre el tratamiento intra-articular de estanozolol micronizado en caballos con osteoartritis, con el objetivo de analizar su aplicabilidad en la práctica de la medicina equina. El estanozolol es un derivado sintético de la testosterona. En la terapia humana se utiliza actualmente en varias condiciones clínicas, como para estimular la eritropoyesis en algunas formas de anemia. Los estudios sugieren que este fármaco tiene propiedades antiinflamatorias, reduce la apoptosis en los caballos condrocitos por el agotamiento de la producción de óxido nítrico y el factor de crecimiento estimulante como la insulina, estimula la proliferación de osteoblastos y la producción de crecimiento de la matriz ósea y los factores de síntesis. IL-1previniendo la degeneración del componente mineral. Se han realizado varios experimentos en caballos para evaluar el comportamiento micronizado del estanozolol en la articulación media y su influencia en la enfermedad degenerativa de las articulaciones. Al final de esta revisión de la literatura se puede concluir que el estanozolol micronizado cuando se utiliza repetidamente a dosis intraarticular 5 mg en una articulación con signos agudos de osteoartritis o crónica, logró diminuir el nivel de claudicación animal, así como reducir los cambios morfológicos y mejorar Sinovial en atletas equinos, justificando su uso como fármaco antiartrítico.
Assuntos
Animais , Cavalos , Estanozolol/uso terapêutico , Osteoartrite/terapia , Osteoartrite/veterinária , Anti-InflamatóriosRESUMO
Elevated concentrations of testosterone and its synthetic analogs may induce changes in cardiovascular function. However, the effects of the combination of anabolic/androgenic steroid (AAS) treatment and exercise training on systolic and diastolic cardiac function are poorly understood. In the present study, we aimed to investigate the effects of low-dose steroid treatment (stanozolol) on cardiac contractile parameters when this steroid treatment was combined with exercise training in rats and the effects of chronic steroid treatment on the Frank-Starling (length-tension curves) relationship. Male Wistar rats were randomly assigned to one of four groups: U (untrained), US (untrained and treated with stanozolol 5 mg/kg/week), T (trained, 16 m/min/1 h) and TS (trained and treated with stanozolol 5 mg/kg/week). Continuous exercise training was conducted 5 days/week for 8 consecutive weeks. The speed of the treadmill was gradually increased to a final setting of 16 m/min/1 h. Experiments were divided into two independent series: 1) central hemodynamic analysis for mean arterial blood pressure (MAP) and cardiac output (CO) measurements and 2) isolated papillary muscle preparation in Krebs solution. Stanozolol treatment significantly increased the MAP and the heart size in untrained and trained rats (U 113±2; T 106±2; US 138±8 and TS 130±7 mmHg). Furthermore, stanozolol significantly decreased developed tension and dT/dt (maximal and minimal) in U rats. However, the developed tension was completely restored by training. The Frank/Starling relationship was impaired in rats treated with stanozolol; however, again, training completely restored diastolic function. Taken together, the present data suggest that AAS treatment is able to decrease cardiac performance (systolic and diastolic functions). The combination of stanozolol and physical training improved cardiac performance, including diastolic and systolic functions, independent of changes in central hemodynamic parameters. Therefore, changes in ventricular myocyte calcium transients may play a cardioprotective role.
Assuntos
Anabolizantes/farmacologia , Teste de Esforço/métodos , Coração/efeitos dos fármacos , Miocárdio/patologia , Estanozolol/farmacologia , Animais , Pressão Sanguínea , Débito Cardíaco , Frequência Cardíaca/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Hematócrito , Hemodinâmica/efeitos dos fármacos , Masculino , Contração Miocárdica/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Condicionamento Físico Animal , Ratos , Ratos Wistar , Esteroides/farmacologiaRESUMO
The aim of the present study was to evaluate DNA damage (micronucleus) and cellular death (pyknosis, karyolysis and karyorrhexis) in exfoliated buccal mucosa cells from anabolic steroid users after 2 months of exposure. Two experimental groups consisting of 15 adult males who practise weight lifting and are anabolic steroid users or 15 adult males who practise weight lifting, but are non-anabolic steroid users, were recruited. In addition, 20 sedentary males, who do not practise any physical activity regularly, were matched by age with experimental groups. No significant statistical differences (p>0.05) were noticed in individuals who practise physical activity only. On the other hand, an increase of micronucleated cells (MNCs) in anabolic steroid (decadurabulin and Winstrol) users was observed. Regarding cytotoxic parameters, the same observation has occurred, that is, significant statistical differences (p<0.05) were noticed in the group exposed to anabolic steroids when compared with other controls, as depicted by high frequencies of pyknosis, karyolysis and karyorrhexis. Taken together, our results suggest that genomic instability and cytotoxicity are induced by anabolic steroid administration in oral mucosa cells as assessed by the micronucleus test.