Anabolic steroids and their effects of on neuronal density in cortical areas and hippocampus of mice / Esteroides anabolizantes e seus efeitos na densidade neuronal em áreas corticais e no hipocampo de camundongos

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.

Anabolic steroids and their effects of on neuronal density in cortical areas and hippocampus of mice.

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.

Multiple hepatocellular adenomas associated with long-term administration of androgenic steroids for aplastic anemia: A case report and literature review.

INTRODUCTION: Anabolic steroids are widely administered to patients with aplastic anemia (AA) and are associated with numerous medical complications. To assist with future diagnoses, we report about a young boy with multiple hepatocellular adenomas (HAs) induced by long-term use of anabolic androgenic steroids (AAS) for AA and present a related literature review. PATIENT CONCERN: A 15-year-old boy who was diagnosed with AA in 2011 had been treated with stanozolol (6 mg per day) and ciclosporin A (120-150 mg per day) for almost 4 years. He presented with epigastric pain and fever, and abdominal computed tomography showed a lesion of heterogenous density measuring 13.5 × 13.0 × 8.0 cm in the left hepatic lobe, which was initially misdiagnosed as a liver abscess. DIAGNOSIS: The patient went into hemorrhagic shock twice after invasive manipulation that aimed at diagnosis and was finally diagnosed with HA using fine needle aspiration. INTERVENTIONS: The patient discontinued AAS and only reserved ciclosporin A for AA treatment. OUTCOMES: Follow-up abdominal computed tomography performed 4 years after AAS discontinuation showed obvious regression of the hepatic lesions. CONCLUSION: It is of great importance for hematologists to completely understand that the long-term use of AAS may cause HA, which carries a great risk of hemorrhage and malignant transformation.

Death after misuse of anabolic substances (clenbuterol, stanozolol and metandienone).

A 34-year old male was found breathless and panting at home by his girlfriend three hours after a gym workout. Minutes later, he collapsed and died. Autopsy, histological and chemical analyses were conducted. The examination of the heart showed left ventricular hypertrophy, while the right coronary artery showed only a small vascular lumen (3 mm in diameter), due to its anatomical structure. In femoral blood concentrations of approx. 1 µg/L clenbuterol, approx. 56 µg/L stanozolol and approx. 8 µg/L metandienone, with trenbolone (

Colestasis canalicular inducida por anabolizantes esteroideos / Canalicular cholestasis induced by anabolic steroids

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Impacts of dose and time of boldenone and stanazolol exposure in inflammatory markers, oxidative and nitrosative stress and histopathological changes in the rat testes.

The present study was conducted to analyze the adverse effects of the anabolic steroids boldenone (BOL) and stanazolol (ST) in the reproductive function of male rats. These molecules were administered using three different protocols. In Protocol I, BOL and ST were administered in a higher dose than what is recommended but for a short period. In Protocol II, a moderate dose of these compounds was applied for an intermediate period, whereas in Protocol III a reduced dose was administered but for an extended period. Notably, Protocol I and III resulted in increased levels of reactive oxygen specimens (ROS [I, p < 0.01] [III, p < 0.001)]) and nitrite plus nitrate (NOx [I, p < 0.01] [II, p < 0.01] [III,p < 0.05]), respectively, whereas non-protein thiols (NPSH) levels were decreased only after Protocol III (p < 0.01). Myeloperoxidase activity was significantly increased after treatment with BOL in protocol II (p < 0.01) and III (p < 0.05) than with ST in protocol III (p < 0.05). Boldenone and ST also caused a significant up-regulation in the levels of serum testosterone when protocols I (p < 0.01) and II (p < 0.05) were performed. There were also visible histopathological alterations in the testes induced by treatment with BOL, namely degenerative changes primarily characterized by a decrease in the germinal epithelium. Together, these results suggest that the administration of BOL or ST exerts a significantly harmful effect in the testes of male rats. Moreover, all the treatment protocols used in this study induced deleterious effects on the testes, as indicated by the different biochemical parameters investigated. However, only the protocols of longer exposure time (II and III) induced morphological changes compatible with infertility.

Blood biochemical and oxidant/antioxidant alterations following stanozolol treatment along with resistance training in rats.

This study was designed to determine the effects of anabolic steroid stanozolol (ST) in conjunction with 8 weeks of resistance training on some blood biochemical and oxidant/antioxidant profile in rats. Twenty-four male rats were divided into four groups of six each: group 1: sedentary + placebo (physiological saline), group 2: training + placebo, group 3: training + ST (2 mg kg-1 b.w.) and group 4: training + ST (5 mg kg-1 b.w.). Erythrocytic activity of glutathione peroxidase was increased significantly in group 4 as compared to control group. Plasma activities of alanine aminotransferase in groups 3 and 4 and also aspartate aminotransferase in group 4 showed significant increase relative to groups 1 and 2. Moreover, alkaline phosphatase and creatine kinase activities increased significantly in groups 3 and 4 in comparison with control group. Elevated values of uric acid were significant in group 4, but not in groups 2 and 3, as compared to control group. Values of other measured parameters did not have significant alterations among experimental groups. Present findings indicate that stanozolol treatment in combination with resistance training induces some side effects especially on liver and muscle as evidenced by alterations in plasma markers of tissue damage.

Acute bile nephropathy secondary to anabolic steroids.

Renal dysfunction in cholestatic liver disease is multifactorial. Acute kidney injury may develop secondary to renal vasoconstriction in the setting of peripheral vasodilation and relative hypovolemia, tubular obstruction by bile casts, and direct tubular toxicity from bile. Anabolic steroids are frequently used by athletes to boost endurance and increase muscle mass. These agents are a recently recognized cause of hepatotoxicity and jaundice and may lead to acute kidney injury. To increase awareness about this growing problem and to characterize the pathology of acute kidney injury in this setting, we report on a young male who developed acute kidney injury in the setting of severe cholestatic jaundice related to ingestion of anabolic steroids used for bodybuilding. Kidney biopsy showed bile casts within distal tubular lumina, filamentous bile inclusions within tubular cells, and signs of acute tubular injury. This report supports the recently re-emerged concept of bile nephropathy cholemic nephrosis.

Fatal Liver Cyst Rupture Due to Anabolic Steroid Use: A Case Presentation.

Liver cysts are commonly found incidentally from imaging scans or at autopsy. These benign neoplasms vary in size and represent a heterogeneous group of disorders, for which the demographics, risk factors, apparent inciting event, clinical presentation, and outcome are varied. Complications that can develop from a liver cyst include development of spontaneous hemorrhage, infection, and/or obstruction. Although the etiology of liver cysts varies, fatal rupture of a hemorrhagic liver cyst due to anabolic steroid use is a rare occurrence. In fact, there are few reported cases in journal literature. We report a case of a fatal liver cyst rupture with resultant hemoperitoneum in the presence of anabolic steroid (stanozolol) use.

Bile cast nephropathy due to cholestatic jaundice after using stanozolol in 2 amateur bodybuilders.

Elevated level of bile can cause bile cast nephropathy, which can be seen in patients with severe cholestatic liver disease. Stanozolol is a C17α-alkylation steroid derived from dihydrotestosterone and its major adverse effect is cholestatic jaundice. We report 2 bodybuilders who received stanozolol for 6 weeks and developed icterus. Serum total bilirubin was around 50 mg/dL. Liver biopsy showed intrahepatic cholestasis. In spite of fluid and albumin therapy, serum creatinine increased and the patients experienced oliguria. Urine sediment showed granular cast and normal erythrocyte count. Protein excretion in 24-hour urine was less than 1000 mg in both patients. Hemodialysis was started on and renal biopsy revealed acute tubular epithelial cell damage along with bile pigment (cast) deposition, compatible with bile cast-related nephropathy. Serum bilirubin decreased gradually and urine output increased. Serum creatinine was around 1.5 mg/dL in both of the patients 2 months after discharge.

Critical appraisal of androgen use in hereditary angioedema: a systematic review.

OBJECTIVE: To provide an objective basis for evaluating the risk-benefit ratio of long-term androgen use in patients with hereditary angioedema (HAE). DATA SOURCES: PubMed was searched with no time limitations using the keywords hereditary angioedema or angio-oedema combined with danazol, stanozolol, and androgen. STUDY SELECTION: Qualifying articles were English-language reports of androgen use in patients with HAE, with relevant safety and/or efficacy information. Reports were categorized according to level of evidence (LOE). RESULTS: The search process identified 153 citations, 63 of which contained relevant information; 2 additional publications were identified while other citations were being reviewed. Fifteen LOE 2 studies and multiple LOE 4 reports provided efficacy data, confirming a high level of prophylactic efficacy for androgen therapy in HAE, with occasional reports of poor prophylactic response. Common adverse events include weight gain, menstrual irregularities, virilization, headaches, myalgias or cramps, mood changes, and elevations in creatine phosphokinase level, liver function test results, and serum lipid level. The risk of adverse events is often correlated with dose and/or treatment duration. Rare cases of hepatic adenomas and hepatocellular carcinoma associated with long-term androgen use often had no preceding changes in liver function test results. CONCLUSION: Androgen therapy may be effective for most patients with HAE; however, potential risks and adverse effects must be carefully considered and discussed with patients when considering options for long-term HAE prophylaxis.

Severe alkalosis and hypokalemia with stanozolol misuse.

Stanozolol is a popular androgenic anabolic steroid, used by body builders and athletes for physical performance enhancement. There are few data on its potential adverse effects and no documented cases of it causing severe electrolyte imbalance. Here, we report a patient presenting to a tertiary care emergency department with reduced conscious level, profound hypokalemia, and severe metabolic alkalosis, resulting from stanozolol misuse. This is the first such case reported.

Stanozolol-induced bland cholestasis

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[Ingestion of anabolic steroids and ischaemic stroke. A clinical case report and review of the literature]. / Ingesta de esteroides anabolizantes e ictus isquemico. Presentacion de un caso clinico y revision de la bibliografia.

INTRODUCTION. Anabolic-androgenic steroids are synthetic substances derived from testosterone that are employed for their trophic effect on muscle tissue, among other uses. Their consumption can give trigger a series of adverse side effects on the body, including the suppression of the hypothalamus-pituitary-gonadal axis as well as liver, psychiatric and cardiovascular disorders. The most common effects are altered fat profiles and blood pressure values, cardiac remodelling, arrhythmias or myocardial infarcts. CASE REPORT. We report the case of a young male, with a background of anabolic-androgenic steroids abuse, who visited because of an acute neurological focus in the right hemisphere related with an ischaemic stroke. The aetiological study, including cardiac monitoring, echocardiograph and imaging studies (magnetic resonance and arteriography) and lab findings (thrombophilia, serology, autoimmunity, tumour markers) showed no alterations. CONCLUSIONS. The association between consumption of anabolic-androgenic steroids and cardiovascular pathologies is known, but its relation with cerebrovascular disease has not received so much attention from researchers.

Brain nerve growth factor unbalance induced by anabolic androgenic steroids in rats.

PURPOSE: Anabolic androgenic steroids (AAS) are synthetic androgen-like compounds that are abused in sport communities despite their adverse effects. Nerve growth factor (NGF) influences neuronal differentiation and survival, and it also mediates higher brain functions such as learning and memory. Changes in NGF expression have been implicated in neurodegenerative disorders, including Alzheimer disease. Hence, we decided to study the effect of chronic AAS exposure on brain NGF profile, NGF-dependent cholinergic function, and related behavioral performance. METHODS: Male Wistar rats were injected for 4 wk with either nandrolone or stanozolol at daily doses (5.0 mg·kg(-1), s.c.) that are considered equivalent to those abused by humans. NGF levels and NGF receptor (TrkA and p75NTR) expression were measured in the hippocampus and in the basal forebrain. Choline acetyltransferase expression was evaluated in basal forebrain. Spatial learning and memory were assessed using the Morris water maze. RESULTS: AAS treatment caused region-specific changes in the expression of NGF and its receptors. Both nandrolone and stanozolol increased NGF levels in the hippocampus and reduced NGF levels in the basal forebrain, reduced p75NTR expression in the hippocampus, and failed to affect TrkA expression in the basal forebrain. Finally, AAS treatment reduced the expression of choline acetyltransferase in the basal forebrain and impaired the behavioral performance in the Morris water maze. CONCLUSION: The evidence that supraphysiological doses of AAS cause neurotrophic unbalance and related behavioral disturbances raises the concern that AAS abuse in humans may affect mechanisms that lie at the core of neuronal plasticity.

Neurochemical consequence of steroid abuse: stanozolol-induced monoaminergic changes.

An extensive literature has documented adverse effects on mental health in anabolic androgenic steroids (AAS) abusers. Depression seems a common adverse reaction in AAS abusers. Recently it has been reported that in a rat model of AAS abuse stanozolol induces behavioural and biochemical changes related to the pathophysiology of major depressive disorder. In the present study, we used the model of AAS abuse to examine possible changes in the monoaminergic system, a neurobiological substrate of depression, in different brain areas of stanozolol-treated animals. Wistar rats received repeated injections of stanozolol (5mg/kg, s.c.), or vehicle (propylene glycol, 1ml/kg) once daily for 4weeks. Twenty-four hours after last injection, changes of dopamine (DA) and relative metabolite levels, homovanilic acid (HVA) and 3,4-dihydroxy phenylacetic acid (DOPAC), serotonin (5-HT) and its metabolite levels, 5-hydroxy indolacetic acid (5-HIAA), and noradrenaline (NA) amount were investigated in prefrontal cortex (PFC), nucleus accumbens (NAC), striatum (STR) and hippocampus (HIPP). The analysis of data showed that after chronic stanozolol, DA levels were increased in the HIPP and decreased in the PFC. No significant changes were observed in the STR or in the NAC. 5-HT and 5-HIAA levels were decreased in all brain areas investigated after stanozolol exposure; however, the 5-HIAA/5-HT ratio was not altered. Taken together, our data indicate that chronic use of stanozolol significantly affects brain monoamines leading to neurochemical modifications possibly involved in depression and stress-related states.

Nandrolone and stanozolol induce Leydig cell tumor proliferation through an estrogen-dependent mechanism involving IGF-I system.

Several substances such as anabolic androgenic steroids (AAS), peptide hormones like insulin-like growth factor-I (IGF-I), aromatase inhibitors and estrogen antagonists are offered via the Internet, and are assumed without considering the potential deleterious effects that can be caused by their administration. In this study we aimed to determine if nandrolone and stanozolol, two commonly used AAS, could have an effect on Leydig cell tumor proliferation and if their effects could be potentiated by the concomitant use of IGF-I. Using a rat Leydig tumor cell line, R2C cells, as experimental model we found that nandrolone and stanozolol caused a dose-dependent induction of aromatase expression and estradiol (E2) production. When used in combination with IGF-I they were more effective than single molecules in inducing aromatase expression. AAS exhibited estrogenic activity and induced rapid estrogen receptor (ER)-dependent pathways involving IGF1R, AKT, and ERK1/2 phosphorylation. Inhibitors for these kinases decreased AAS-dependent aromatase expression. Up-regulated aromatase levels and related E2 production increased cell proliferation as a consequence of increased cyclin E expression. The observation that ER antagonist ICI182,780 was also able to significantly reduce ASS- and AAS + IGF-induced cell proliferation, confirmed a role for estrogens in AAS-dependent proliferative effects. Taken together these data clearly indicate that the use of high doses of AAS, as it occurs in doping practice, enhances Leydig cell proliferation, increasing the risk of tumor development. This risk is higher when AAS are used in association with IGF-I. To our knowledge this is the first report directly associating AAS and testicular cancer.

Rhabdomyolysis of the deltoid muscle in a bodybuilder using anabolic-androgenic steroids: a case report.

OBJECTIVE: Rhabdomyolysis (breakdown of skeletal muscle tissue) may be caused by mechanical, physical, chemical, or biological factors. We present the unique case of a bodybuilder who developed localized rhabdomyolysis of the deltoid muscle after injection of steroids into the shoulder region. BACKGROUND: A 39-year-old amateur bodybuilder presented to the emergency department with excruciating pain and inability to move his right shoulder after injecting stanozolol, an anabolic-androgenic steroid (AAS), into his right deltoid muscle on the same day. On physical examination, the right deltoid muscle was swollen and tense and the surrounding skin red, tender, and warm. He had no fluctuation or systemic fever and no sensory or motor deficit. His distal pulsations were distinct. Laboratory test results suggested massive rhabdomyolysis. The major magnetic resonance imaging finding was diffuse hyperintensity signals on T2-weighted images of the deltoid muscle, which was consistent with edema. DIFFERENTIAL DIAGNOSIS: Polymyositis and dermatomyositis, mild injury, infectious myositis without phlegmon or abscess formation, radiation therapy, subacute denervation, compartment syndrome, early myositis ossificans, rhabdomyolysis, and sickle cell crisis. TREATMENT: The patient was treated with intravenous fluid replacement and sodium bicarbonate to alkalinize the urine. Four days after admission, his pain had decreased, he had regained range of motion, and his renal function remained unaffected. UNIQUENESS: Anabolic-androgenic steroid use is associated with various side effects that are generally systemic and dose related. We could not find reports of localized side effects of AAS use, as this case presented, elsewhere in the English-language literature. CONCLUSIONS: "Doping" among amateur athletes occurs frequently. It can cause acute and chronic health problems, most of which are systemic. This is the first description of localized rhabdomyolysis in the area of an AAS injection.