Nandrolone Supplementation Promotes AMPK Activation and Divergent 18[FDG] PET Brain Connectivity in Adult and Aged Mice.

Decreased anabolic androgen levels are followed by impaired brain energy support and sensing with loss of neural connectivity during physiological aging, providing a neurobiological basis for hormone supplementation. Here, we investigated whether nandrolone decanoate (ND) administration mediates hypothalamic AMPK activation and glucose metabolism, thus affecting metabolic connectivity in brain areas of adult and aged mice. Metabolic interconnected brain areas of rodents can be detected by positron emission tomography using 18FDG-mPET. Albino CF1 mice at 3 and 18 months of age were separated into 4 groups that received daily subcutaneous injections of either ND (15 mg/kg) or vehicle for 15 days. At the in vivo baseline and on the 14th day, brain 18FDG-microPET scans were performed. Hypothalamic pAMPKT172/AMPK protein levels were assessed, and basal mitochondrial respiratory states were evaluated in synaptosomes. A metabolic connectivity network between brain areas was estimated based on 18FDG uptake. We found that ND increased the pAMPKT172/AMPK ratio in both adult and aged mice but increased 18FDG uptake and mitochondrial basal respiration only in adult mice. Furthermore, ND triggered rearrangement in the metabolic connectivity of adult mice and aged mice compared to age-matched controls. Altogether, our findings suggest that ND promotes hypothalamic AMPK activation, and distinct glucose metabolism and metabolic connectivity rearrangements in the brains of adult and aged mice.

[Administration of Anabolic Steroids in Combination with Vitamin D in the Early Stage of Treatment of Polytrauma Patients - a Dead End?] / Aplikace anabolických steroidu s vitaminem D v casné fázi lécby polytraumatizovaných pacientu ­ slepá ulicka?

PURPOSE OF THE STUDY Persistent catabolism is one of the main causes of delayed healing in polytrauma patients. The purpose of this study is to verify the effect of early administration of an anabolic steroid in combination with vitamin D on the process of bone healing in polytrauma patients. MATERIAL AND METHODS In this prospective study, the patients with a serious trauma were divided into two groups (a control group and a treatment group), with the treatment group being treated with nandrolone decanoate, an anabolic steroid in combination with vitamin D. In all the patients, bone metabolism markers and sex hormone levels (men only) were monitored through lab testing for the period of 70 days and the results of both the groups were subsequently compared. RESULTS The study included a total of 64 patients, 32 in the control group and 32 in the treatment group. The differences between the groups in gender (p = 0.387) as well as in the age of patients (p = 0.436) were statistically non-significant. There was a significant difference in the Injury Severity Score (48 in the treatment group as against 41 in the control group, p = 0.022). Even though this difference was statistically significant, it cannot be considered clinically significant since all the patients met the major trauma criteria. No positive effect of this treatment on bone metabolism parameters was established; on the very contrary, the only statistically significant changes were observed in the control group. To be specific, in levels of one of the bone formation markers, bone alkaline phosphatase on Day 7 after the injury (an increased level in the control group; p = 0.002) and in one of the bone resorption markers (bone acid phosphatase) on Day 70 after the injury (an increased level in the treatment group; p = 0.042). In the treatment group, 70 days after the injury a higher 25(OH)vitamin D level (p < 0.001) was reported and starting from Day 7 in men in the treatment group a significantly lower testosterone level and free testosterone level were observed. The level of androgenic hormones dramatically dropped in both the groups during the first days after the trauma, the dynamics of its normalization was faster in patients in the control group than in the treatment group. DISCUSSION The administration of nandrolone decanoate, an anabolic steroid, in combination with vitamin D did not produce the expected effect, i.e. an improvement in bone healing markers in polytrauma patients. One would expect that in polytrauma patients with a bone fracture or fractures during bone healing higher levels of all the markers of bone resorption as well as bone formation will persist. Similar increases in bone metabolism levels, however, were observed also in patients with injuries in other somatic regions. This indicates the importance of bone tissue involvement in the overall response of the organism to polytrauma. A faster normalization of the levels of testosterone, dihydrotestosterone and free testosterone in the control group compared to the treatment group corresponds with the supplemental effect of anabolic steroids and reduced production of these hormones as a feedback to hypothalamic-pituitary-adrenal axis. CONCLUSIONS In the follow-up period, the positive effect of anabolic steroid and vitamin D administration on bone metabolism in polytrauma patients was not confirmed. Key words: polytrauma, anabolic steroids, vitamin D, bone metabolism.

Anabolic steroid excess promotes hydroelectrolytic and autonomic imbalance in adult male rats: Is it enough to alter blood pressure?

AIM: The present study investigated the effects of anabolic steroid (AS) excess on blood pressure regulation. METHODS: Male Wistar rats were treated with nandrolone decanoate (AS) or vehicle (CTL) for 8 or 10 weeks. Saline (1.8%) and water intake were measured in metabolic cages. Urinary volume, osmolarity, Na+ and K+ concentrations, and plasma osmolarity were measured. The autonomic balance was estimated by heart rate variability at baseline or after icv injection of losartan. Cardiac function was assessed by echocardiography and ex vivo recordings. Myocardial collagen deposition was evaluated by Picrosirius-Red staining. Vascular reactivity and wall thickness were investigated in aortic sections. Blood pressure (BP) was assessed by tail-cuff plethysmography. Angiotensin II type I receptor (AT1R), renin, and mineralocorticoid receptor (MR) mRNA expression was measured in the kidneys and whole hypothalamus. RESULTS: AS group exhibited decreased urinary volume and Na+ concentration, while urinary K+ concentration, plasma osmolarity, and renal AT1R and renin mRNA levels were increased compared to CTL (p < 0.05). Water intake was increased, and saline intake was decreased in the AS group (p < 0.01). AS group exhibited increased low-frequency/high-frequency-ratio, while it was decreased by icv injection of losartan (p < 0.05) compared to baseline. Neither cardiac function nor vascular reactivity/morphology was affected by AS excess (p > 0.05). Ultimately, BP levels were not altered by AS excess (p > 0.05). CONCLUSION: AS excess promoted hydroelectrolytic and autonomic imbalance but did not alter vascular or cardiac function/morphology.

Cynara scolymus leaves extract alleviates nandrolone decanoate-induced alterations in testicular function and sperm quality in albino rats.

Nandrolone decanoate (ND) is a commonly used anabolic-androgenic steroid. These drugs are illegally self-administered by athletes to enhance their sports performance. However, their abuse could influence the testicular function and fertility. The main objective of this study was to evaluate the possible protective effects of Cynara scolymus leaf extract (CLE) on ND-induced testicular dysfunction in rats. Five groups of adult male rats (10 rats each) were used. Group I rats received only saline and served as controls. Group II rats were injected with a vehicle once weekly, while group III rats received intramuscular injections of ND (20 mg/kg/week for 60 days). Group IV rats orally received 1 g/kg/day of CLE and group V rats received ND and CLE at the aforementioned doses. The results revealed that ND has a negative impact on the testicular function as evidenced by the significant increases (p ≤ 0.05) in testicular malondialdehyde concentration and serum non-prostatic acid phosphatase activity, as well as the significant decreases in serum testosterone levels, testicular weight, glutathione concentration, catalase enzyme activity, and total antioxidant capacity. These results were accompanied by considerable alterations of sperm characters and histopathological studies of the testicular tissue. However, co-treatment with CLE extract significantly alleviated (p ≤ 0.05) almost all ND-induced pathological alterations. In conclusion, co-treatment of ND-intoxicated rats with CLE ameliorated the toxic effects of ND on the testicular structure and function, probably due to its antioxidant activity.

Preliminary effect and feasibility of physiotherapy with strength training and protein-rich nutritional supplement in combination with anabolic steroids in cross-continuum rehabilitation of patients with hip fracture: protocol for a blinded randomized controlled pilot trial (HIP-SAP1 trial).

BACKGROUND: A 2014 Cochrane review evaluating the effect of anabolic steroids after hip fracture concluded that the quality of the studies was insufficient to draw conclusions on the effects and recommended further high-quality trials in the field. Therefore, the aim of this pilot trial is to determine the preliminary effect and feasibility of a 12-week multimodal intervention consisting of physiotherapy (with strength training), protein-rich nutritional supplement and anabolic steroid on knee-extension muscle strength and function 14 weeks after hip fracture surgery. METHODS: We plan to conduct a randomized, placebo-controlled pilot trial with 48 patients operated for acute hip fracture. The patients are randomized (1:1) to either (1) physiotherapy with protein-rich nutritional supplement plus anabolic steroid or (2) physiotherapy with protein-rich nutritional supplement plus placebo. Outcome assessments will be carried out blinded at baseline (3-10 days after surgery) and at 14 weeks after entering the trial. Primary outcome is the change from baseline to follow-up in maximal isometric knee-extension muscle strength in the fractured limb. Secondary outcomes are physical performance test, patient-reported outcomes, and measures of body composition. DISCUSSION: If the trial is found feasible and the results show an indication of anabolic steroid being a relevant addition to further enhance the recovery of muscle strength and function in an enhanced recovery after surgery program, this trial will constitute the basis of a larger confirmatory trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03545347. Preregistered on 4 June 2018.

Lipid Profile Changes Induced by Chronic Administration of Anabolic Androgenic Steroids and Taurine in Rats.

Background and Objectives: Anabolic androgenic steroids (AAS), used as a therapy in various diseases and abused in sports, are atherogenic in supraphysiological administration, altering the plasma lipid profile. Taurine, a conditionally-essential amino acid often used in dietary supplements, was acknowledged to delay the onset and progression of atherogenesis, and to mitigate hyperlipidemia. The aim of the present study was to verify if taurine could prevent the alterations induced by concomitant chronic administration of high doses of AAS nandrolone decanoate (DECA) in rats. Materials and Methods: Thirty-two male Wistar rats, assigned to 4 equal groups, were treated for 12 weeks either with DECA (A group), taurine (T group), both DECA and taurine (AT group) or vehicle (C group). Plasma triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), hepatic triglycerides (TGh) and liver non-esterified fatty acids (NEFA) were then determined. Results: DECA elevated TG level in A group vs. control (p = 0.01), an increase prevented by taurine association in AT group (p = 0.04). DECA decreased HDL-C in A group vs. control (p = 0.02), while taurine tended to increase it in AT group. DECA decreased TGh (p = 0.02) in A group vs. control. Taurine decreased TGh in T (p = 0.004) and AT (p < 0.001) groups vs. control and tended to lower NEFA (p = 0.08) in AT group vs. A group. Neither DECA, nor taurine influenced TC and LDL-C levels. Conclusions: Taurine partially prevented the occurrence of DECA negative effects on lipid profile, suggesting a therapeutic potential in several conditions associated with chronic high levels of plasma androgens, such as endocrine disorders or AAS-abuse.

Long-term treatment with Nandrolone Decanoate impairs mesenteric vascular relaxation in both sedentary and exercised female rats.

Nandrolone Decanoate (ND) is an Anabolic Androgenic Steroid (AAS) that under abusive regimen can lead to multiple physiological adverse effects. Studies of AAS-mediated cardiovascular (CV) alterations were mostly taken from male subjects, even though women are also susceptible to the effects of AAS and gender-specific differences in susceptibility to vascular diseases exist. Here we investigate ND-induced vascular reactivity alterations in both sedentary and exercised female rats and whether these alterations depend on endothelium-derived factors. We show that chronic exposure of female Wistar rats to ND (20mg/Kg/week for 4weeks) impaired the vascular mesenteric bed (MVB) reactivity to vasodilator (acetylcholine) agonist. The endothelium-dependent Nitric Oxide (NO) component was reduced in ND-treated rats, whereas neither the endothelium-derived hyperpolarizing factor (EDHF) component nor prostanoids were altered in the MVBs. Endothelial dysfunction observed in ND-treated rats was associated with decreased eNOS (Ser1177) and Akt (Ser473) phosphorylation sites and upregulation of iNOS and NADPH oxidase expression. Exercise training by weight lifting in water did not improve the vascular alterations induced by ND treatment. ND treatment also significantly reduced the serum levels of estradiol in females, overriding its CV protective effect. These results help uncover the role of ND modulating endothelial function in the setting of CV disease caused by the abuse of AAS in females. If this translates to humans, young women abusing AAS can potentially lose the cardio protective effect rendered by estrogen and be more susceptible to CV alterations.

Impact of chronic administration of anabolic androgenic steroids and taurine on blood pressure in rats.

Supraphysiological administration of anabolic androgenic steroids has been linked to increased blood pressure. The widely distributed amino acid taurine seems to be an effective depressor agent in drug-induced hypertension. The purpose of this study was to assess the impact of chronic high dose administration of nandrolone decanoate (DECA) and taurine on blood pressure in rats and to verify the potentially involved mechanisms. The study was conducted in 4 groups of 8 adult male Wistar rats, aged 14 weeks, treated for 12 weeks with: DECA (A group); vehicle (C group); taurine (T group), or with both drugs (AT group). Systolic blood pressure (SBP) was measured at the beginning of the study (SBP1), 2 (SBP2) and 3 months (SBP3) later. Plasma angiotensin-converting enzyme (ACE) activity and plasma end products of nitric oxide metabolism (NOx) were also determined. SBP3 and SBP2 were significantly increased compared to SBP1 only in the A group (P<0.002 for both). SBP2, SBP3 and ACE activity showed a statistically significant increase in the A vs C (P<0.005), andvs AT groups (P<0.05), while NOx was significantly decreased in the A and AT groups vs controls (P=0.01). ACE activity was strongly correlated with SBP3 in the A group (r=0.71, P=0.04). These findings suggest that oral supplementation of taurine may prevent the increase in SBP induced by DECA, an effect potentially mediated by angiotensin-converting enzyme.

Impact of single-dose nandrolone decanoate on gonadotropins, blood lipids and HMG CoA reductase in healthy men.

The aim was to study the effect and time profile of a single dose of nandrolone decanoate (ND) on gonadotropins, blood lipids and HMG CoA reductase [3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR)] in healthy men. Eleven healthy male participants aged 29-46 years were given a single dose of 150 mg ND as an intramuscular dose of Deca Durabol®, Organon. Blood samples for sex hormones, lipids and HMGCR mRNA analysis were collected prior to ND administration day 0, 4 and 14. A significant suppression of luteinising hormone (LH) and follicle-stimulating hormone (FSH) was seen after 4 days. Total testosterone and bioavailable testosterone level decreased significantly throughout the observed study period. A small but significant decrease in sexual hormone-binding globulin (SHBG) was seen after 4 days but not after 14 days. Total serum (S)-cholesterol and plasma (P)-apolipoprotein B (ApoB) increased significantly after 14 days. In 80% of the individuals, the HMGCR mRNA level was increased 4 days after the ND administration. Our results show that a single dose of 150 mg ND increases (1) HMGCR mRNA expression, (2) total S-cholesterol and (3) P-ApoB level. The long-term consequences on cardiovascular risk that may appear in users remain to be elucidated.

Fundamental understanding of drug absorption from a parenteral oil depot.

Oil depots are parenteral drug formulations meant for sustained release of lipophilic compounds. Until now, a comprehensive understanding of the mechanism of drug absorption from oil depots is lacking. The aim of this paper was to fill this gap. A clinical study with healthy volunteers was conducted. An oil depot with nandrolone decanoate and benzyl alcohol was subcutaneously administered in the upper arm of female volunteers. Pharmacokinetic profiles of both substances were related to each other and to literature data. Benzyl alcohol absorbs much more rapidly than nandrolone. In detail, it appears that benzyl alcohol enters the central compartment directly, while nandrolone decanoate is recovered in serum after a lag time. This lag time is also seen in literature data, although not reported explicitly. The absorption of nandrolone is enhanced by the presence of benzyl alcohol. This is most likely an effect of altered oil viscosity and partition coefficient between the oil and aqueous phase. The absorption rate constant of compounds is found to be related to the logP of the solubilized prodrug. The absorption rate is however not only determined by the physico-chemical properties of the formulation but also by the tissue properties. Here, it is argued that lymphatic flow must be considered as a relevant parameter.

Cardiotoxicity in rabbits after long-term nandrolone decanoate administration.

Abuse of anabolic androgenic steroids is linked to a variety of cardiovascular complications. The aim of our study was to investigate the possible cardiovascular effects of nandrolone decanoate on young rabbits using echocardiography, histology and monitoring of telomerase activity, oxidative stress and biochemical markers. Fourteen rabbits were divided into three administration groups and the control group. Doses of 4mg/kg and 10mg/kg of nandrolone decanoate, given intramuscularly and subcutaneously, two days per week for six months were applied. A 4-months wash-out period followed. Focal fibrosis and inflammatory infiltrations of cardiac tissue were observed in the high dose groups. Thiobarbituric acid-reactive species (TBARS) levels were significantly increased in the high dose groups, while catalase activity decreased. Myocardial Performance Index (MPI) is the main echocardiographic index primarily affected by nandrolone administration in rabbits. Despite the preserved systolic performance, histological lesions observed associated with distorted MPI values, point to diastolic impairment of the thickened myocardium due to nandrolone treatment. Oxidative stress accumulates and telomerase activity in cardiac tissue rises. Subcutaneous administration seems to be more deleterious to the cardiovascular system, as oxidative stress, telomerase activity and biochemical markers do not appear to return into normal values in the wash-out period.

Anabolic steroids for rehabilitation after hip fracture in older people.

BACKGROUND: Hip fracture occurs predominantly in older people, many of whom are frail and undernourished. After hip fracture surgery and rehabilitation, most patients experience a decline in mobility and function. Anabolic steroids, the synthetic derivatives of the male hormone testosterone, have been used in combination with exercise to improve muscle mass and strength in athletes. They may have similar effects in older people who are recovering from hip fracture. OBJECTIVES: To examine the effects (primarily in terms of functional outcome and adverse events) of anabolic steroids after surgical treatment of hip fracture in older people. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (10 September 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2013 Issue 8), MEDLINE (1946 to August Week 4 2013), EMBASE (1974 to 2013 Week 36), trial registers, conference proceedings, and reference lists of relevant articles. The search was run in September 2013. SELECTION CRITERIA: Randomised controlled trials of anabolic steroids given after hip fracture surgery, in inpatient or outpatient settings, to improve physical functioning in older patients with hip fracture. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials (based on predefined inclusion criteria), extracted data and assessed each study's risk of bias. A third review author moderated disagreements. Only very limited pooling of data was possible. The primary outcomes were function (for example, independence in mobility and activities of daily living) and adverse events, including mortality. MAIN RESULTS: We screened 1290 records and found only three trials involving 154 female participants, all of whom were aged above 65 years and had had hip fracture surgery. All studies had methodological shortcomings that placed them at high or unclear risk of bias. Because of this high risk of bias, imprecise results and likelihood of publication bias, we judged the quality of the evidence for all primary outcomes to be very low.These trials tested two comparisons. One trial had three groups and contributed data to both comparisons. None of the trials reported on patient acceptability of the intervention.Two very different trials compared anabolic steroid versus control (no anabolic steroid or placebo). One trial compared anabolic steroid injections (given weekly until discharge from hospital or four weeks, whichever came first) versus placebo injections in 29 "frail elderly females". This found very low quality evidence of little difference between the two groups in the numbers discharged to a higher level of care or dead (one person in the control group died) (8/15 versus 10/14; risk ratio (RR) 0.75, 95% confidence interval (CI) 0.42 to 1.33; P = 0.32), time to independent mobilisation or individual adverse events. The second trial compared anabolic steroid injections (every three weeks for six months) and daily protein supplementation versus daily protein supplementation alone in 40 "lean elderly women" who were followed up for one year after surgery. This trial provided very low quality evidence that anabolic steroid may result in less dependency, assessed in terms of being either dependent in at least two functions or dead (one person in the control group died) at six and 12 months, but the result was also compatible with no difference or an increase in dependency (dependent in at least two levels of function or dead at 12 months: 1/17 versus 5/19; RR 0.22, 95% CI 0.03 to 1.73; P = 0.15). The trial found no evidence of between-group differences in individual adverse events.Two trials compared anabolic steroids combined with another nutritional intervention ('steroid plus') versus control (no 'steroid plus'). One trial compared anabolic steroid injections every three weeks for 12 months in combination with daily supplement of vitamin D and calcium versus calcium only in 63 women who were living independently at home. The other trial compared anabolic steroid injections every three weeks for six months and daily protein supplementation versus control in 40 "lean elderly women". Both trials found some evidence of better function in the steroid plus group. One trial reported greater independence, higher Harris hip scores and gait speeds in the steroid plus group at 12 months. The second trial found fewer participants in the anabolic steroid group were either dependent in at least two functions, including bathing, or dead at six and 12 months (one person in the control group died) (1/17 versus 7/18; RR 0.15, 95% CI 0.02 to 1.10; P = 0.06). Pooled mortality data (2/51 versus 3/51) from the two trials showed no evidence of a difference between the two groups at one year. Similarly, there was no evidence of between-group differences in individual adverse events. Three participants in the steroid group of one trial reported side effects of hoarseness and increased facial hair. The other trial reported better quality of life in the steroid plus group. AUTHORS' CONCLUSIONS: The available evidence is insufficient to draw conclusions on the effects, primarily in terms of functional outcome and adverse events, of anabolic steroids, either separately or in combination with nutritional supplements, after surgical treatment of hip fracture in older people. Given that the available data points to the potential for more promising outcomes with a combined anabolic steroid and nutritional supplement intervention, we suggest that future research should focus on evaluating this combination.

Study of body composition, lung function, and quality of life following use of anabolic steroids in patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow limitation and is associated with weight loss and decreased muscle strength and exercise capacity. METHODS: A double-blinded randomized controlled trial of 32 male COPD patients (age, 54.94 ± 11.27 years) was carried out to assess effects of anabolic steroid in terms of a daily high-protein, high-calorie diet alone or one combined with anabolic steroids on body composition, lung function, and health-related quality of life (HRQL). Outcomes were assessed by anthropometric and spirometric measurements, peak expiratory flow rate, partial pressure of oxygen in arterial blood, 6-minute walk test (6MWT), hand grip test, and HRQL index scores. Measurements were made at baseline and end of treatment (6 weeks). RESULTS: All patients showed significant difference (P < .001) in pulmonary function parameters and anthropometric measurements after 6 weeks of intervention (within-group changes); however, no significant improvement occurred in the pulmonary function parameters between the groups. The difference in exercise capacity (6MWT) and HRQL scores in the treatment group were statistically significant (P < .001) compared with control group after 6 weeks of intervention. In the treatment group, the average 6MWT distance increased from 213.5 m to 268.5 m at 6-week follow-up, and HRQL scores increased from 101.25 to 118.45. Also, HRQL and 6MWT parameters were positively correlated in response to steroid supplementation at the end of the study. CONCLUSION: Weekly administration of anabolic steroids during 6 weeks increased exercise capacity and quality of life in patients with COPD.

[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.

The blockade of angiotensin AT1 and aldosterone receptors protects rats from synthetic androgen-induced cardiac autonomic dysfunction.

AIM: This study aimed to evaluate the combined effects of exercise and antagonists of the angiotensin II and aldosterone receptors on cardiac autonomic regulation and ventricular repolarization in rats chronically treated with nandrolone decanoate (ND), a synthetic androgen. METHODS: Thirty male Wistar rats were divided into six groups: sedentary, trained, ND-treated, trained and ND-treated, trained and treated with both ND and spironolactone, and trained and treated with both ND and losartan. ND (10 mg kg(-1) weekly) and the antagonists (20 mg kg(-1) daily) of the angiotensin II AT1 (losartan) and aldosterone (spironolactone) receptors were administered for 8 weeks. Exercise training was performed using a treadmill five times each week for 8 weeks. Following this 8-week training and treatment period, electrocardiogram recordings were obtained to determine the time and frequency domains of heart rate variability (HRV) and corrected QT interval (QTc). RESULTS: Nandrolone decanoate treatment increased the QTc interval and reduced the parasympathetic indexes of HRV (RMSSD, pNN5 and high-frequency power) in sedentary and trained rats. The ratio between low- and high-frequency power (LF/HF) was higher in ND-treated groups. Both losartan and spironolactone treatments prevented the effects of ND on the QTc interval and the HRV parameters (RMSSD, pNN5, high-frequency power, and the LF/HF ratio). CONCLUSION: Our results show that chronic treatment with a high dose of ND induces cardiac parasympathetic dysfunction and disturbances in ventricular repolarization in both sedentary and exercised rats. Furthermore, inhibiting the renin-angiotensin-aldosterone system using losartan, or spironolactone, prevented these deleterious effects.

Influence of chronic administration of anabolic androgenic steroids and taurine on haemostasis profile in rats: a thrombelastographic study.

Anabolic androgenic steroids (AAS) are synthetic derivatives of testosterone with thrombogenic potential in high doses and long-term administration. Taurine, a widely distributed amino-sulfonic acid, is known for its beneficial effects in hypercoagulable states. In order to assess the impact of chronic administration of high doses of AAS and taurine upon haemostasis process in rats, 40 male Wistar rats were divided into four equal groups: control group (group C) - no treatment; androgen group (group A) - received 10 mg/kg per week of nandrolone decanoate (DECA); taurine (group T) - received oral supplementation of 2% taurine in drinking water; androgen and taurine group (group AT) - concomitant administration of DECA and taurine. After 12 weeks, blood samples were collected and haemostasis parameters were assessed with the thrombelastographic (TEG) analysis system: reaction time, clot kinetics (K, α), final clot strength, coagulation index and the clot lysis (Ly30). Nandrolone significantly decreased reaction time in group A compared with control (P<0.001), whereas taurine significantly increase reaction time (P=0.01), and this effect was maintained in group AT compared with group A (P=0.009). Similar differences between groups have been recorded for the clot kinetics parameters K, α. The final clot strength and coagulation index were significantly increased in group A versus group C (P=0.04, respectively P<0.001), but not in group AT versus group C (P>0.05). There were no differences in clot lysis, as shown by Ly30. Nandrolone produces an accelerated clot development and an increased clot firmness in Wistar rats. Taurine association ensures a protective effect against this hypercoagulable state, partially restoring the altered parameters of the coagulation profile.

Nandrolone androgenic hormone presents genotoxic effects in different cells of mice.

Nandrolone is an androgenic-anabolic steroid (AAS) with diverse medical applications but taken indiscriminately by some to rapidly increase muscle mass. The aim of this study was to evaluate the genotoxic and clastogenic potential of nandrolone (deca-durabolin®) in vivo in different cells of mice, using the comet assay and micronucleus test, respectively. The animals received subcutaneous injection of the three doses of the steroid (1.0, 2.5 and 5.0 mg kg⁻¹ body weight). Cytotoxicity was assessed by scoring 200 consecutive total polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE-NCE ratio). The results showed a significant dose-related increase in the frequency of DNA damage in leukocytes, liver, bone marrow, brain and testicle cells at the three tested doses and a significant increase of the micronucleated polychromatic erythrocytes at all tested doses. Under our experimental conditions, the nandrolone steroid hormone showed genotoxic and clastogenic effects when administered subcutaneously to mice.

Effect of low-level laser therapy on proliferation, differentiation, and adhesion of steroid-treated osteoblasts.

There has recently been constant effort to evaluate therapies that may have a positive effect on bone regeneration. However, there are few studies in the literature on the effects of low-level laser therapy (LLLT) involving tissues treated with anabolic steroids. The present study evaluated the effects of LLLT (AsGaAl 780 nm, 3 J/cm(2), 10 mW, beam spot of 0.04 cm(2), total energy 0.12 J) on the proliferation, adhesion, and differentiation of osteoblasts cultured in the presence of nandrolone decanoate (ND). The MTT method was employed to evaluate cell proliferation and adhesion. Cell differentiation was evaluated by measuring alkaline phosphatase activity. There was a significant decrease in cell proliferation in the irradiated group treated with 50 µM ND when compared to the control group, after 48 h. After 72 h, cell proliferation was significantly greater in the control group than in the irradiated groups treated with the steroid at concentrations of 10, 25, and 50 µM. With regard to cell differentiation, alkaline phosphatase activity was significantly higher in the irradiated group treated with 50 µM ND than in the control group, irradiated non-treated group, and irradiated group treated with 25 µM ND. After 60 min of plating, the irradiated non-treated group and irradiated groups treated with the steroid at concentrations of 5, 10, and 25 µM exhibited a significant increase in cell adhesion compared to the control group. LLLT in combination with a high concentration of steroid inhibited cell proliferation, possibly by inducing cell differentiation, while irradiation combined with lower concentrations of the steroid induced an increase in cell adhesion.

Developmental and withdrawal effects of adolescent AAS exposure on the glutamatergic system in hamsters.

In the Syrian hamster (Mesocricetus auratus) glutamate activity has been implicated in the modulation of adolescent anabolic-androgenic steroid (AAS)-induced aggression. The current study investigated the time course of adolescent AAS-induced neurodevelopmental and withdrawal effects on the glutamatergic system and examined whether these changes paralleled those of adolescent AAS-induced aggression. Glutamate activity in brain areas comprising the aggression circuit in hamsters and aggression levels were examined following 1, 2, 3, and 4 weeks of AAS treatment or 1, 2, 3, and 4 weeks following the cessation of AAS exposure. In these studies glutamate activity was examined using vesicular glutamate transporter 2 (VGLUT2). The onset of aggression was observed following 2 weeks exposure to AAS and continued to increase showing maximal aggression levels after 4 weeks of AAS treatment. This aggressive phenotype was detected after 2 weeks of withdrawal from AAS. The time-course of AAS-induced changes in latero-anterior hypothalamus (LAH)-VGLUT2 closely paralleled increases in aggression. Increases in LAH-VGLUT2 were first detected in animals exposed to AAS for 2 weeks and were maintained up to 3 weeks following the cessation of AAS treatment. AAS treatment also produced developmental and long-term alterations in VGLUT2 expression within other aggression areas. However, AAS-induced changes in glutamate activity within these regions did not coincide with changes in aggression. Together, these data indicate that adolescent AAS treatment leads to alterations in the glutamatergic system in brain areas implicated in aggression control, yet only alterations in LAH-glutamate parallel the time course of AAS-induced changes in the aggressive phenotype.

Chronic administration of the anabolic androgenic steroid nandrolone alters neurosteroid action at the sigma-1 receptor but not at the sigma-2 or NMDA receptors.

Studies have shown that anabolic androgenic steroids (AASs) can induce profound changes to mental health. Commonly reported psychiatric side effects among AAS users include aggression, anxiety, depression, drug abuse and cognitive disabilities. In experimental animals, many of these effects have been associated with alterations in a number of neurotransmitter systems. We have observed that chronic administration of the AAS nandrolone (nandrolone decanoate) can affect excitatory amino acids as well as monoaminergic and peptidergic pathways in a way that is compatible with nandrolone-induced behavioural changes. The aim of the present work was to further explore the mechanisms underlying nandrolone-induced effects, with a particular focus on components known to be involved in aggression and cognitive function. Male rats were given daily injections of nandrolone decanoate for 14 days and the effects on neurosteroid interactions with sites on the N-methyl-D-aspartyl (NMDA) and sigma receptors were examined. These receptors were chosen because of their involvement in aggressive and cognitive behaviors and the hypothesis that nandrolone might affect the brain via interaction with neurosteroids. Radiolabelled [³H]ifenprodil was used in the binding studies because of its significant affinity for the NMDA and sigma receptors. The results indicated that [³H]ifenprodil binds to both sigma-1 and sigma-2 sites and can be displaced to a certain extent from both sites by the neurosteroids pregnenolone sulphate (PS), pregnanolone sulphate (3α5ßS) and dehydroepiandrosterone sulphate (DHEAS). The remainder of the [³H]ifenprodil was displaced from the sigma-1 site by the sigma-1 receptor-selective ligand (+)-SKF 10,047. Chronic nandrolone treatment changed the sigma-1 receptor target for the neurosteroids but not for ifenprodil. The sigma-2 receptor site was unaltered by treatment with nandrolone decanoate. The results also indicated that the neurosteroid-induced allosteric modulation of the NMDA receptor subunit NR2B was not affected by nandrolone treatment. We conclude that chronic treatment with nandrolone changes the affinity of the neurosteroids PS, 3α5ßS and DHEAS at the sigma-1 site but not at the sites on the sigma-2 receptor or the NMDA receptor subunit NR2B.