Supraphysiological Doses Of Anabolic Androgenic Steroids Research Articles

Effects of Nandrolone Decanoate on Skeletal Muscle and Neuromuscular Junction of Sedentary and Exercised Rats.

Background and Objectives: Nandrolone decanoate (ND) is the most widely used among the anabolic androgenic steroids (AAS), synthetic substances derived from testosterone, to improve muscular and health gains associated with exercises. The AAS leads to physical performance enhancement and presents anti-aging properties, but its abuse is associated with several adverse effects. Supraphysiological doses of AAS with or without physical exercise can cause morphological and functional alterations in neuromuscular interactions. This study aims to investigate the effects of ND supraphysiological doses in neuromuscular interactions, focusing on the soleus muscle and its neuromuscular junctions (NMJs) in rats, associated or not with physical exercise. Materials and Methods: Forty male Sprague Dawley rats were divided into four groups: sedentary and exercised groups, with or without ND at the dose of 10 mg/kg/week. The animals were treated for eight weeks, with intramuscular injections, and the soleus muscle was collected for morphological analyses. Results: The supraphysiological doses of ND in the sedentary group caused muscle degeneration, evidenced by splitting fibers, clusters of small fibers, irregular myofibrils, altered sarcomeres, an increase in collagen deposition and in the number of type I muscle fibers (slow-twitch) and central nuclei, as well as a decrease in fibers with peripheral nuclei. On the other hand, in the ND exercise group, there was an increase in the NMJs diameter with scattering of its acetylcholine receptors, although no major morphological changes were found in the skeletal muscle. Thus, the alterations caused by ND in sedentary rats were partially reversed by physical exercise. Conclusions: The supraphysiological ND exposure in the sedentary rats promoted an increase in muscle oxidative pattern and adverse morphological alterations in skeletal muscle, resulting from damage or post-injury regeneration. In the ND-exercised rats, no major morphological changes were found. Thus, the physical exercise partially reversed the alterations caused by ND in sedentary rats.

Anabolic androgenic steroids and cardiomyopathy: an update.

Anabolic androgenic steroids (AAS) include endogenously produced androgens like testosterone and their synthetic derivatives. Their influence on multiple metabolic pathways across organ systems results in an extensive side effect profile. From creating an atherogenic and prothrombotic milieu to direct myocardial injury, the effects of AAS on the heart may culminate with patients requiring thorough cardiac evaluation and multi-disciplinary medical management related to cardiomyopathy and heart failure (HF). Supraphysiological doses of AAS have been shown to induce cardiomyopathy via biventricular dysfunction. Advancement in imaging including cardiac magnetic resonance imaging (MRI) and additional diagnostic testing have facilitated the identification of AAS-induced left ventricular dysfunction, but data regarding the impact on right ventricular function remains limited. Emerging studies showed conflicting data regarding the reversibility of AAS-induced cardiomyopathy. There is an unmet need for a systematic long-term outcomes study to empirically evaluate the clinical course of cardiomyopathy and to assess potential targeted therapy as appropriate. In this review, we provide an overview of the epidemiology, pathophysiology and management considerations related to AAS and cardiomyopathy.

Effect of Supra-Physiological Doses of Anabolic-Androgenic Steroids on the Neuronal Density of the Central and Basolateral Amygdala in Mice

Anabolic-androgenic steroids (AAS), despite being controlled by government agencies, are illegally marketed and heavily consumed among youngsters that want a lean, muscular appearance and improved physical performance. Behavioral changes mediated by the amygdala, such as depression, aggressiveness and anxiety, are reported among users. The main scope of this work is to quantify the number of neuron cells on the nuclei of the central (CA) and basolateral (BLA) mice's amygdala submitted to a chronic supra-physiological doses of Durateston® (a combination of testosterone propionate, testosterone isocaproate and testosterone decanoate) and Deca Durabolin® (nandrolone decanoate), administered isolated and combined. For this purpose, 40 Swiss male mice were taken and divided into 4 (four) groups (n = 10): a control group (C), in which mice received saline solution; a Dura group, in which mice received Durateston®; a Deca group, in which mice received Deca Durabolin®; and a Dura-Deca group, in which mice received both drugs. Mice were treated with AAS for a period of 60 days and underwent exercises (swimming). After this time, mice were euthanized and had their brains removed. The material thus obtained was processed in a conventional histological routine. For the neuron cells quantitative analyses, the simple random sampling count method was used. The results showed that there was a significant decrease in the number of neuron cells in all AAS treated animals comparing to the control group; concerning the amygdala basolateral nucleus, the decrease ranged from 23% to 36%, according to the AAS selected group; regarding the amygdala central nucleus, the decrease ranged from 20% to 29%, according to the AAS selected group. One can conclude that the administration of supra-physiological doses of these AAS causes decrease in the number of neuron cells on the central and basolateral nuclei of Swiss male mice's amygdala.

Differential protein expression profile in the hypothalamic GT1-7 cell line after exposure to anabolic androgenic steroids.

The abuse of anabolic androgenic steroids (AAS) has been considered a major public health problem during decades. Supraphysiological doses of AAS may lead to a variety of neuroendocrine problems. Precisely, the hypothalamic-pituitary-gonadal (HPG) axis is one of the body systems that is mainly influenced by steroidal hormones. Fluctuations of the hormonal milieu result in alterations of reproductive function, which are made through changes in hypothalamic neurons expressing gonadotropin-releasing hormone (GnRH). In fact, previous studies have shown that AAS modulate the activity of these neurons through steroid-sensitive afferents. To increase knowledge about the cellular mechanisms induced by AAS in GnRH neurons, we performed proteomic analyses of the murine hypothalamic GT1-7 cell line after exposure to 17α-methyltestosterone (17α-meT; 1 μM). These cells represent a good model for studying regulatory processes because they exhibit the typical characteristics of GnRH neurons, and respond to compounds that modulate GnRH in vivo. Two-dimensional difference in gel electrophoresis (2D-DIGE) and mass spectrometry analyses identified a total of 17 different proteins that were significantly affected by supraphysiological levels of AAS. Furthermore, pathway analyses showed that modulated proteins were mainly associated to glucose metabolism, drug detoxification, stress response and cell cycle. Validation of many of these proteins, such as GSTM1, ERH, GAPDH, PEBP1 and PDIA6, were confirmed by western blotting. We further demonstrated that AAS exposure decreased expression of estrogen receptors and GnRH, while two important signaling pathway proteins p-ERK, and p-p38, were modulated. Our results suggest that steroids have the capacity to directly affect the neuroendocrine system by modulating key cellular processes for the control of reproductive function.

Exogenous Supraphysiological Doses of Anabolic-Androgenic Steroids: Controversial and Reciprocal Effects on Performance and Organs

Exogenous Supraphysiological Doses of Anabolic-Androgenic Steroids: Controversial and Reciprocal Effects on Performance and Organs

Exercise-induced cardioprotection is impaired by anabolic steroid treatment through a redox-dependent mechanism

High doses of anabolic androgenic steroids (AAS) impair the cardioprotective effects of exercise against ischemia/reperfusion (I/R) insult, possibly through cellular redox imbalance. Here, the effect of nandrolone decanoate (DECA) treatment on heart redox metabolism was investigated during I/R in sedentary and exercised rats. DECA treatment significantly reduced superoxide dismutase and glutathione reductase activities in exercised rats after heart reperfusion. Catalase and glutathione peroxidase activities were not affected by DECA in both sedentary and trained rats, regardless the I/R period. DECA also induced myocardial oxidative stress, as evidenced by the reduced levels of total reduced thiols after heart reperfusion in exercised rats treated with the anabolic steroid. These results indicate that cardiotoxic effects of supraphysiological doses of AAS involve reduced heart antioxidant capacity.

Brain Nerve Growth Factor Unbalance Induced by Anabolic Androgenic Steroids in Rats

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. 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. 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. 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.

Anabolic-androgenic steroid induced alterations in choline acetyltransferase messenger RNA levels of spinal cord motoneurons in the male rat

The effect of chronic supraphysiological doses of anabolic-androgenic steroids, such as those illegally used by recreational, amateur and professional athletes to increase muscle mass and strength, on motoneurons has not been established. The choline acetyltransferase activity levels of perineal muscles in the male rat are modulated by plasma testosterone levels. These muscles are innervated by the sexually dimorphic motoneurons of the spinal nucleus of the bulbocavernosus. Since the primary source of choline acetyltransferase in muscle is motoneuronal, testosterone may modulate perineal muscle choline acetyltransferase activity by regulating choline acetyltransferase messenger RNA levels in motoneurons. The purpose of this study was to determine if choline acetyltransferase messenger RNA levels in cervical and lumbar spinal motoneurons are affected by chronic (four weeks) changes of plasma testosterone levels in the adult male rat. Using in situ hybridization, choline acetyltransferase messenger RNA levels were analysed in four motor columns: the spinal nucleus of the bulbocavernosus, the retrodorsal lateral nucleus of the lumbar spinal cord, and the lumbar lateral motor columns of the cervical and lumbar spinal cords. Chronic exposure to supraphysiological levels of testosterone (five- to ten-times physiologic levels) significantly increased choline acetyltransferase messenger RNA in all four motor columns. Subsequent to castration, choline acetyltransferase messenger RNA levels decreased in motoneurons of the spinal nucleus of the bulbocavernosus and the retrodorsal lateral nucleus. This observation suggests that the decrease in choline acetyltransferase activity levels of muscles innervated by spinal nucleus of the bulbocavernosus motoneurons may be due to changes in choline acetyltransferase protein levels. Indeed, testosterone replacement therapy of castrated males prevented the decline of choline acetyltransferase messenger RNA levels in motoneurons.The results of this study demonstrate that anabolic-androgenic steroids can affect the levels of specific messenger RNAs in motoneuron populations throughout the spinal cord suggesting that motoneuronal characteristics are modulated by circulating anabolic-androgenic steroid levels regardless of the purported “androgen sensitivity” of the specific neuromuscular system.