Nandrolone Decanoate Administration Research Articles

Unveiling the Impact of Nandrolone Decanoate on Kidney and Heart of Rattus Norvegicus

Background: The use of anabolic androgenic steroids (AAS) like Nandrolone Decanoate (ND) for enhancing physical performance and muscle growth is prevalent among athletes and non-athletes. However, the adverse effects of AAS on organ systems, particularly the kidney and heart, have been a growing concern within the medical and scientific community. Previous studies have highlighted the potential nephrotoxic and cardiotoxic effects of these substances, necessitating further research to elucidate the extent of organ damage. Objective: This study aims to investigate the histopathological effects of ND on the kidney and heart tissues of Rattus norvegicus and to draw comparisons with control groups to assess the severity of organ damage. Methods: A total of 15 Rattus norvegicus were divided into three groups: a control group, an olive oil group (positive control), and a steroid group (ND treated). The animals were housed under controlled conditions with a 12-hour light/dark cycle at 23±2°C. The steroid and olive oil groups received 50mg/ml intramuscular injections of ND and olive oil, respectively, twice weekly for six weeks. Following treatment, the animals were euthanized, and their kidney and heart tissues were extracted for histological examination. Tissues were fixed in 10% formalin, processed, and stained with Hematoxylin and Eosin (H&E) for microscopic evaluation. Results: Histological analysis revealed significant alterations in the ND-treated group compared to controls. Kidney tissues from the ND group exhibited tubular dilation, epithelial degeneration, and necrosis with a noticeable increase in Bowman's space and vascular congestion. Quantitatively, tubular atrophy and degeneration were observed in 80% of the ND-treated animals, compared to none in the control and olive oil groups. Heart tissues in the ND group showed evidence of myocardial fibrosis and necrosis, with myocardial fibrosis observed in 70% of the steroid-treated animals, significantly higher than the control groups. Conclusion: The administration of Nandrolone Decanoate in Rattus norvegicus significantly impacts kidney and heart histology, underscoring the potential health risks associated with AAS use. These findings contribute to the growing body of evidence on the nephrotoxic and cardiotoxic effects of steroids, emphasizing the need for caution and further research in human healthcare to develop safer therapeutic alternatives.

The Role of Androgen Receptors in Mediation of Nandrolone Effects on Spatial Memory and Neuronal Response of Pyramidal Neurons in the Hippocampal CA1 Area

Background: Previously we have reported that intracerebroventricular microinjection of nandrolone decanoate (ND) improves spatial memory and hippocampal synaptic plasticity, but the underlying mechanism has not been clearly evaluated. The aim of this study was evaluated the role of androgen receptors (ARs) in the mediation of ND effects on spatial memory and neuronal response of pyramidal neurons of the hippocampal CA1 area. Materials and Methods: In the current study, the rats were divided into four groups: the control group received DMSO, while other experimental groups received ND (60 μg/2.5 μL), nilutamide (5 μg/2.5 μL), and co-administration of nilutamide (5 μg/2.5 μL) + ND (60 μg/2.5 μL) for 4 days. Spatial learning and memory were evaluated through the Morris water maze (MWM) test. Moreover, we test the electrophysiological properties of hippocampal plasticity by in vitro field potential recordings. In electrophysiological investigations, the field excitatory postsynaptic potentials (fEPSPs) and population spikes were recorded from the hippocampal slices taken from different groups. Results: At the behavioral level, our studies exhibited that escape latency and traveled distance in ND-treated rats significantly decreased during the MWM test’s training period, whereas administration of nilutamide before ND had no significant effect on escape latency and traveled distance in the MWM task. Furthermore, the results of field potential recording showed that the magnitude of fEPSP-long-term potentiation (LTP) of the ND-treated group was higher than the control group, while preadministration of nilutamide abolished the ND improvement effect on the magnitude of fEPSP-LTP. Conclusion: This study suggests that the administration of ND induces improvement in spatial memory and hippocampal synaptic plasticity through activation of central ARs.

The effect of supraphysiological dose of nandrolone decanoate administration on the inflammatory, neurotrophin and behavioral response in adult and old male mice

This study examined the effect of 6 weeks of supraphysiological nandrolone decanoate (ND) administration in adult mice (7 months) on cognitive function and neuroinflammation during aging. Male C57BL/6 mice were randomized into ND (10 mg·kg−1·wk−1) or control (CTL) groups. Half of the mice were tested at a young (Y) age (ND-Y and CTL-Y), 1 week following final ND administration, while the remaining mice were tested at 16 months (O) (ND-O and CTL-O). Learning and memory were better in young mice compared to older mice, regardless of treatment. ND-O displayed decreased anxiety as compared to all other groups. TNFα and IL1β expression were higher in older mice, regardless of treatment. ND administration in young mice appeared to attenuate the neuroinflammatory response in aging mice as evidenced by decreased COX2, IL-4 and increased IL-10 expression in ND-O compared to CTL-O. BDNF AR and ER expression increased in ND-O compared to CTL-O. Results of the study indicated that supraphysiological ND administration had no negative effect on learning and memory but may attenuate anxiety in older mice. In addition, ND administration in young adult mice may attenuate the inflammatory response during aging, which may be related to elevations in both AR and ER expression.

Adenosine receptors participate in anabolic-androgenic steroid-induced changes on risk assessment/anxiety-like behaviors in male and female rats

Anabolic-androgenic steroids (AAS) and caffeine can induce several behavioral alterations in humans and rodents. Administration of nandrolone decanoate is known to affect defensive responses to aversive stimuli, generally decreasing inhibitory control and increasing aggressivity but whether caffeine intake influences behavioral changes induced by AAS is unknown. The present study aimed to investigate behavioral effects of caffeine (a non-selective antagonist of adenosine receptors) alone or combined with nandrolone decanoate (one of the most commonly AAS abused) in female and male Lister Hooded rats. Our results indicated that chronic administration of nandrolone decanoate (10 mg/kg, i.m., once a week for 8 weeks) decreased risk assessment/anxiety-like behaviors (in the elevated plus maze test), regardless of sex. These effects were prevented by combined caffeine intake (0.1 g/L, p.o., ad libitum). Overall, the present study heralds a key role for caffeine intake in the modulation of nandrolone decanoate-induced behavioral changes in rats, suggesting adenosine receptors as candidate targets to manage impact of AAS on brain function and behavior.

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 18months of age were separated into 4 groups that received daily subcutaneous injections of either ND (15mg/kg) or vehicle for 15days. 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.

Nandrolone supplementation does not improve functional recovery in an aged animal model of volumetric muscle loss injury.

Aging hinders the effectiveness of regenerative medicine strategies targeting the repair of volumetric muscle loss (VML) injury. Anabolic steroids have been shown to improve several factors which contribute to the age-related decline in muscle's regenerative capacity. In this study, the impact of exogenous nandrolone decanoate (ND) administration on the effectiveness of a VML regenerative repair strategy was explored using an aged animal model. Unilateral tibialis anterior VML injuries were repaired in 18-month-aged animal models (male Fischer 344 rat) using decellularized human skeletal muscle scaffolds supplemented with autologous minced muscle. The contralateral limb was left untreated/uninjured. Following repair, ND(+) or a carrier control (ND-) was delivered via weekly injection for a period of 8weeks. At 8weeks, muscle isometric torque, gene expression, and tissue structure were assessed. ND(+) treatment did not improve contractile torque recovery following VML repair when compared to carrier only ND(-) injection controls. Peak isometric torque in the ND(+) VML repair group remained significantly below contralateral uninjured control values (4.69±1.18vs. 7.46±1.53N mm/kg) and was statistically indistinguishable from carrier only ND(-) VML repair controls (4.47±1.18N mm/kg). Gene expression for key myogenic genes (Pax7, MyoD, MyoG, IGF-1) were not significantly elevated in response to ND injection, suggesting continued age related myogenic impairment even in the presence of ND(+) treatment. ND injection did reduce the histological appearance of fibrosis at the site of VML repair, and increased expression of the collagen III gene, suggesting some positive effects on repair site matrix regulation. Overall, the results presented in this study suggest that a decline in regenerative capacity with aging may present an obstacle to regenerative medicine strategies targeting VML injury and that the delivery of anabolic stimuli via ND administration was unable to overcome this decline.

Interaction of high-intensity endurance exercise and nandrolone on cardiac remodeling: role of adipo-cardiac axis.

Given the cardiac pathological remodeling following to anabolic androgenic steroids (AASs) consumption, we examined the effect of chronic administration of nandrolone decanoate with high-intensity endurance exercise on the left ventricular hypertrophy index, levels of hydroxyproline, tumor necrosis factor-alpha (TNF-α), adiponectin (APN) and its receptors (AdipoR1 and AdipoR2) expression in rats' hearts. The male Wistar rats randomly divided to six groups included the control (CTL), exercise (Ex), nandrolone (Nan), vehicle (Arach), trained vehicle (Ex+Arach), and trained nandrolone (Ex+Nan) groups that were treated for eight weeks. Nandrolone consumption significantly enhanced the hypertrophy index (p<0.05) and exercise intensified this effect. It also increased the level of cardiac hydroxyproline (p<0.001), however exercise completely masked this effect. The values of TNF-α protein and AdipoR1 protein significantly increased in trained nandrolone-treated (Ex+Nan) group in comparison with CTL group (p<0.05), however, did not show significant alteration in Nan or Ex groups. High-intensity endurance exercise significantly enhanced the AdipoR2 protein (p<0.05), but, co-administration of nandrolone with exercise prevented this effect. The mRNA expression of AdipoR1 significantly reduced in the animals that received nandrolone for eight weeks and exercise recovered this effect (p<0.001). Despite an additive effect of high-intensity endurance exercise plus nandrolone on TNF-α level, their effects on hydroxyproline and APN receptors expression is incompatible in heart of rat. It is suggests a part of beneficial regulatory role of endurance exercise against nandrolone induced heart remodeling may apply through modulation of APN system.

Assessment of testicular steroidogenic enzymes expression in experimental animal model following withdrawal of nandrolone decanoate.

Anabolic steroids are frequently used to increase the growth rate of meat-producing animals. Exposure to an anabolic-androgenic steroid, nandrolone decanoate (ND), is associated with expressional reduction of testicular steroidogenic enzymes. However, the effect of withdrawal of ND exposure on the expression of these testicular molecules has not been thoroughly explored. The current research investigated expression changes of testicular steroidogenic enzymes in rats at several recovery periods (2, 6, and 12 weeks) after the stop of ND treatment with different doses (2 and 10 mg/kg body weight) for 12 weeks. Body and testis weights were recorded, and transcript levels of molecules were determined by quantitative real-time polymerase chain reaction (PCR). The immunohistochemistry was used to examine the changes of immuno-intensities of molecules. At 6 and 12 weeks of the recovery period, the 10 mg/kg ND-treated rats were lighter than other experimental groups. The interstitial compartment vanished by ND treatment filled up as the recovery period became longer. The expression of steroidogenic acute regulatory protein was returned to the control level at 12 weeks of the recovery period. Expression levels of cytochrome P450 side-chain cleavage and 17a-hydroxylase were increased in 2 mg/kg ND-treated group at 6 weeks of the recovery period, and transcript levels of these molecules in 2 and 10 mg/kg ND-treated groups at 12 weeks of the recovery period were significantly lower than the control. Expression levels of 3β-hydroxysteroid dehydrogenase (HSD) type I and 17β-HSD type 3 in 2 mg/kg ND-treated group were comparable with those of control at 12 weeks of the recovery period, but not in 10 mg/kg ND-treated group. Expression of cytochrome P450 aromatase (Cyp19) was reverted to the control level at 2 weeks of the recovery period. Except for Cyp19, there was a visible increase of immuno-staining intensity of other testicular steroidogenic enzymes in the Leydig cells as the recovery period progressed. This research has demonstrated that the cease of ND administration could restore the expression of testicular steroidogenic enzymes close to the normal level. Nevertheless, a relatively long recovery period, compared to the ND-exposure period would be required to retrieve normal expression levels of testicular steroidogenic enzymes.

Morphometric analysis and redox state of the testicles in nandrolone decanoate and swimming treated adult male rats

BackgroundDuring the last decades, the abuse of anabolic androgenic steroids (AASs) has become popular among professional and recreational athletes. The abuse of AASs leads to decreased levels of sex hormones, but the available literature a gives very small pool of data regarding the effects of swimming alone or combined with AASs on testicle tissue. The aim of this study was to investigate the effects of four-week administration of nandrolone decanoate and swimming training alone or in combination on morphometric parameters, androgen receptor (AR) and redox state in testicle tissue. The study included Wistar albino male rats, 10 weeks old, classified into 4 groups: control (T-N-), nandrolone (T-N+), swimming training (T+N-) and swimming training with nandrolone (T+N+). The rats from nandrolone (N+) groups received nandrolone decanoate 20 mg/kg b.w.once per week. The rats from training (T+) groups, swam 1 h/day 5 days/week. The isolated testicles were measured, left testicles were routinely processed for histological analysis, while right testicles were homogenized and prepared for the analysis of the following oxidative stress biomarkers: index of lipid peroxidation (TBARS), nitrites, catalase, superoxide dismutase (SOD), and reduced glutathione (GSH).ResultsDiameter, as well as cross-section area of seminiferous tubules were decreased by 10 % and 21 % (respectively) in the T-N+ group and by 15% and 41 % (respectively) in the T+N+ group compared to control. Interstitium of the testicles was decreased in all experimental groups. Reduction of immunoreactivity of AR in T-N+ group was 22 %, in T+N+ group was 9 % compared to control. TBARS levels were increased in T+N- and T+N+ groups. Nitrites were decreased in T+N+ group. Catalase activity was increased in all experimental groups. Swimming alone or combined with nandrolone decreased the level of GSH compared to control. SOD activity was decreased in T-N+ and T+N+ groups compared to control.ConclusionsNandrolone alone or combined with swimming decreased morphometric parameters and amount of AR in testicle tissue. Changes in the redox state indicate reproductive dysfunction.

Nandrolone decanoate causes uterine injury by changing hormone levels and sex steroid receptors in a dose- and time-dependent manner

Different doses of nandrolone decanoate (ND) were used to investigate the expression of uterine sex steroid receptors (AR, ER-α, and ER-β) and the levels of serum sex hormones after treatment and recovery periods in adult rats. ND doses of 1.87, 3.75, 7.5, or 15 mg/kg b.w. or mineral oil (control group) were injected subcutaneously for 15 days, and the experimental groups were divided into three periods of evaluation: (a) ND treatment for 15 days, (b) ND treatment followed by 30-day-recovery and (c) ND treatment followed by 60-day-recovery. Estrous cycle was monitored daily. At the end of each experimental period, rats were euthanized for the collection of serum samples and uterine tissues. All animals showed persistent diestrus and only the highest ND dose was capable of inducing persistent diestrus until 60-day-recovery. Immunoexpression of uterine sex steroid receptors varied in a time-dependent manner. While AR expression was increase after treatment period, ER-α and ER-β expressions decreased after 60- and 30-day-recovery, respectively. ND also increased the serum levels of testosterone, 17β-estradiol, and dihydrotestosterone, especially at the highest doses of 7.5 and 15 mg ND/kg until 30 days of recovery. The levels of progesterone were significantly reduced in all ND-treated animals. No significant difference was observed in the levels of follicle-stimulating hormone, whereas the levels of luteinizing hormone varied according to specific dose and period. We conclude that uterine sex steroid receptors and sex hormones are affected by ND administration and these alterations can be only restored following lower doses and long recovery periods.

Histological and immunohistochemical studies of the effects of administration of anabolic androgenic steroids alone and in concomitant with training exercise on the adult male rats skeletal muscles

Background: Anabolic androgenic steroids (AAS ) abuse is considered as a public issue as a result of their widespread use to enhance muscular building .Aim of the work: The aim of the study is to clarify the hazards effects that occurred in the skeletal muscles of adult male albino rats as a result of administration of Nandrolone Decanoate histologically as well as immunohistochemically and the possible role of the interaction between (AAS) and training exercise . Materials and Methods: Forty adult male albino rats were divided randomly into four groups; group I (control group ) , group II (steroids treated group ), group III (trained group ) and group IV (steroid treated-trained group) . Both groups II and IV were administered 5 mg/kg body weight, of Nandrolone Decanoate twice a week by intramuscular injection for 5weeks. Group III and Group IV were subjected to training protocol in the form of 4 sets of 10 jumps into water for 5 weeks . At the end of the experiments the rats were sacrificed and their quadriceps muscles were processed for histological and immunohistochemically procedures .Results: Group II (steroid treated group) had hypertrophy of muscle fibers and disrupted striations with wide spacing between them. In addition to areas of degeneration and congested blood vessels. Group III had hypertrophy of muscle fibers. Group IV exhibited normal histological appearance of the muscle fibers. Minute areas of focal degeneration and congested blood vessels were observed.Conclusion: Administration of (AAS) was presented with noticeable degenerative changes in the quadriceps muscles of the adult male albino rats . These hazards effects could be attenuated in the group of rats that were subjected to (AAS) in concomitant with training exercise.

Chronic nandrolone decanoate administration effects on antioxidant parameters in Wistar rats

Chronic nandrolone decanoate exposure is associated with a modified redox status in the favor of oxidants. Paraoxonase and myeloperoxidase activities are considered sensitive biomarkers of oxidative stress and inflammation, being also predictors for coronary artery disease. The aim of our study was to investigate the impact of chronic nandrolone administration on paraoxonase and myeloperoxidase activities in Wistar rats. 16 Wistar rats were divided into two groups (n=8 for each of them): nandrolone decanoate (A) treated group and control group (C). After 12 weeks of nandrolone decanoate administration we analyzed several plasma oxidative stress parameters: TROLOX Equivalent Antioxidant Activity, paraoxonase and myeloperoxidase activities, total thiols, and advanced oxidation protein products. Our results showed a significant decreased total antioxidant activity in nandrolone treated group compared with controls, while paraoxonase activity and total thiols levels were significantly increased. Myeloperoxidase activity and advanced oxidation protein products were not significantly different between the two studied groups. In conclusion decreased plasma total antioxidant activity suggested increased oxidative stress induced by chronic high doses of nandrolone. Despite oxidative stress presence high doses of nandrolone induced also increased plasma paraoxonase activity.

Involvement of kynurenine pathway in depressive-like behaviour induced by nandrolone decanoate in mice

Nandrolone decanoate (ND) belongs to the class II of anabolic–androgenic steroids (AAS), which is composed of 19-nor-testosterone-derivatives. AAS represent a group of synthetic testosterone that is used in clinical treatment. However, these drugs are widely abused among individuals as a means of promoting muscle growth or enhancing athletic performance. AAS in general and ND in particular have been associated with several behavioral disturbances, such as anxiety, aggressiveness and depression. A factor that contributes to the development of depression is the brain activation of indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme of kynurenine pathway (KP). In the present study, we examined the involvement of KP in depressive phenotype induced by a ND treatment (10 mg/kg/day/s.c., for 28 days) that mimics human abuse system (e.g. supraphysiological doses) in C57B/6J mice. Our results showed that ND caused depressive like-behavior in the tail suspension test and anhedonic-like state measured in the sucrose preference test. ND administration decreased the levels of brain-derived neurotrophic factor and neurotrophin-3 and reduced Na+,K+-ATPase activity in the hippocampus, striatum and prefrontal cortex. We also found that ND elicited KP activation, as reflected by the increase of IDO activity and kynurenine levels in these brain regions. Moreover, ND decreased serotonin levels and increased 5-hydroxyindoleacetic acid levels in the brain. Treatment with IDO inhibitor 1-methyl-dl-trypthophan (1 mg/kg/i.p.) reversed the behavioral and neurochemical alterations induced by ND. These results indicate for the first time that KP plays a key role in depressive-like behavior and neurotoxicity induced by supraphysiologicaldoses of ND in mice.

Nandrolone decanoate administration does not attenuate muscle atrophy during a short period of disuse.

BackgroundA few days of bed rest or immobilization following injury, disease, or surgery can lead to considerable loss of skeletal muscle mass and strength. It has been speculated that such short, successive periods of muscle disuse may be largely responsible for the age-related loss of muscle mass throughout the lifespan.ObjectiveTo assess whether a single intramuscular injection of nandrolone decanoate prior to immobilization can attenuate the loss of muscle mass and strength in vivo in humans.Design, setting and participantsThirty healthy (22 ± 1 years) men were subjected to 7 days of one-legged knee immobilization by means of a full leg cast with (NAD, n = 15) or without (CON, n = 15) prior intramuscular nandrolone decanoate injection (200 mg).MeasuresBefore and immediately after immobilization, quadriceps muscle cross-sectional area (CSA) (by means of single-slice computed tomography (CT) scans of the upper leg) and one-legged knee extension strength (one-repetition maximum [1-RM]) were assessed for both legs. Furthermore, muscle biopsies from the immobilized leg were taken before and after immobilization to assess type I and type II muscle fiber cross-sectional area.ResultsQuadriceps muscle CSA decreased during immobilization in both CON and NAD (-6 ± 1% and -6 ± 1%, respectively; main effect of time P<0.01), with no differences between the groups (time × treatment interaction, P = 0.59). Leg muscle strength declined following immobilization (-6 ± 2% in CON and -7 ± 3% in NAD; main effect of time, P<0.05), with no differences between groups (time × treatment interaction, P = 0.55).ConclusionsThis is the first study to report that nandrolone decanoate administration does not preserve skeletal muscle mass and strength during a short period of leg immobilization in vivo in humans.

Nandrolone administration abolishes hippocampal fEPSP-PS potentiation and passive avoidance learning of adolescent male rats

Despite the chronic effects of nandrolone decanoate (ND), the acute effects of ND on passive avoidance learning (PAL) and memory and its mechanism have not been investigated. This research examines the acute effect of ND on PAL, CA1 synaptic plasticity, testosterone and corticosterone serum levels, and the role of androgenic receptors (ARs). Adolescent male rats were treated with ND, 30 min before training and retention and after training test. AR antagonist was applied 15 min before ND. Hippocampal slices were perfused by ND. ND administration had an inverted U-shape effect on acquisition of PAL and on testosterone and corticosterone serum levels. The consolidation was only affected by high dose of ND. ND significantly decreased the retention of PAL across all doses. The magnitude of field excitatory postsynaptic potential long term potentiation was lower than that of control slices. In addition, an attenuation of field excitatory postsynaptic potential population spike coupling was also observed. Nilutamide could nullify the ND impairment effect. We concluded although a single dose of ND could affect all stages of PAL, its effects were more potent on retrieval, possibly arising from the acute effect of ND on the alterations of CA1 synaptic plasticity. In addition, ND may induce its effects directly through ARs and indirectly through plasma testosterone and corticosterone.

Investigating the Role of mTORC1 in the Androgen‐Mediated Regulation of Skeletal Muscle Growth

Androgens play an important role in regulating skeletal muscle growth largely through changes in muscle protein balance (synthesis + breakdown). Despite this, the underlying molecular mechanism(s) by which androgens alter protein balance and subsequent muscle growth are poorly defined. Previous research has implicated signaling through the mechanistic target of rapamycin complex 1 (mTORC1) in the androgen‐mediated regulation of protein balance as phosphorylation of mTORC1 substrates that control both protein synthesis and protein breakdown have been shown to be altered by androgen depletion/treatment. However, the role of mTORC1 in the androgen‐mediated regulation of muscle growth in vivo has yet to be defined. To define this role, 10‐week old male mice were randomized into four groups of equal body weight, subjected to a sham or castration surgery, then allowed to recover for 7 weeks to induce muscle atrophy in the castrated groups. Following the recovery, sham and castrated mice were implanted with either a control pellet or a pellet designed to release rapamycin at a rate of ~3 mg/kg of body weight/day over a period of 60 days. One‐week post implantation, a group of castrated mice implanted with either control pellets or rapamycin pellets began receiving weekly, intramuscular injections of nandrolone decanoate (ND) to induce muscle regrowth. All other sham and castrated mice received vehicle only. Mice were treated with vehicle or ND for 6 weeks (42 days). The tibialis anterior (TA) was harvested for analysis. The efficacy of the rapamycin pellets to inhibit mTORC1 was confirmed by the inability of insulin to increase phosphorylation of mTORC1 substrates [i.e. 70 kDa ribosomal protein S6 kinase 1 (Thr389), eIF4E binding protein 1 (Ser65), and uncoordinated like kinase 1(Ser757)] in mice receiving rapamycin even though induction of Akt (Thr308) phosphorylation was unaffected. Castration reduced TA wet weight and muscle fiber cross sectional area (CSA), but these values were restored to sham levels with ND administration, even in the presence of rapamycin. Further, the protein content of the TA was also decreased by castration, and ND administration restored this value to sham levels even in the presence of rapamycin. These changes in protein content were not due to changes in the translational capacity of the muscle as RNA content was similar across treatments. In all, these data indicate that androgens alter protein balance and muscle regrowth in an mTORC1‐independent manner.Support or Funding InformationStart‐up funds from the University of Central FloridaThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Acute interruption of treatment with nandrolone decanoate is not sufficient to reverse cardiac autonomic dysfunction and ventricular repolarization disturbances in rats

Anabolic androgenic steroids are a class of synthetic compounds derived from testosterone, eventually used by athletes, to improve physical performance. However, anabolic steroids can also modify normal cardiovascular function. Thus, we investigated cardiac electrophysiological and autonomic abnormalities in rats, through a electrocardiographic variability protocol during and after interruption of administration of nandrolone decanoate (DECA) anabolic steroid. Twenty male Wistar rats (60–70 days old) received DECA (10 mg. kg−1i.m) once a week or vehicle, during eight weeks. Electrocardiogram was recorded in conscious rats by a noninvasive method, and time and domain analysis of heart rate variability as well as electrocardiogram intervals (QTc / QTd) were performed. Body mass was lower in treated rats compared to control after 4th and 8th weeks, but not at the end of 14th week. QTc and QTd were longer in DECA group compared to control on 4th, 8th, 11th, but equal on 14th week. Cardiac autonomic dysfunction (vagal attenuation) was present on DECA group after 4th week and did not normalize after interruption of treatment. The animals of DECA group showed a correlation between attenuated parasympathetic modulation and increased correct QT interval. Our data allow us to conclude that long-term treatment with DECA impairs autonomic cardiac physiology, predisposing to cardiovascular risk and sudden death, and interruption of administration does not recovery the normality immediately.

Differences of Matrix Metalloproteinase 2 Expression between Left and Right Ventricles in Response to Nandrolone Decanoate and/or Swimming Training in Mice.

Background:Matrix metalloproteinase (MMP)-2 plays an important role in the remodeling of left ventricles (LVs) and right ventricles (RVs). We investigated the differences of MMP-2 expression between LV and RV in response to nandrolone decanoate (ND), swimming training (ST), and combined ND and ST (NS) in mice, based on their structural, functional, and biochemical characteristics.Methods:Totally 28 male C57B1 mice (6 weeks old; 20–23 g) were divided into four groups, including the control (n = 7), ND (n = 6), ST (n = 8), and NS (n = 7) groups. After respective treatments for 8 weeks, echocardiographic examination was used to assess the cardiac structure and function. Van Gieson stain was used to examine the fibrosis of LV and RV in response to different treatments, and Western blotting analysis was performed to explore different MMP-2 expressions between LV and RV in response to ND and/or ST. Analysis of variance was used for comparing the four groups.Results:At 8 weeks, right ventricular dimension/body weight in the ND group was larger than the other three groups (F = 7.12, P < 0.05) according to the echocardiographic examination. Fibrosis induced by ND administration was increased more in RV (2.59%) than that in LV (2.21%). MMP-2 expression of the ND group in RV was significantly greater than the control and NS groups in RV and the corresponding ND group in LV.Conclusion:The experimental data support the hypothesis that ND administration induces greater MMP-2 expression increase in RV compared to LV, leading to consequent RV dilation.

The opposite effects of nandrolone decanoate and exercise on anxiety levels in rats may involve alterations in hippocampal parvalbumin-positive interneurons.

The aim of this study was to evaluate the behavioral effects of chronic (six weeks) nandrolone decanoate (ND, 20 mg/kg, s.c., weekly in single dose) administration (in order to mimic heavy human abuse), and exercise (swimming protocol of 60 minutes a day, five days in a row/two days break), applied alone and simultaneously with ND, in male rats (n = 40). Also, we evaluated the effects of those protocols on hippocampal parvalbumin (PV) content and the possible connection between the alterations in certain parts of hippocampal GABAergic system and behavioral patterns. Both ND and exercise protocols induced increase in testosterone, dihydrotestosterone and estradiol blood levels. Our results confirmed anxiogenic effects of ND observed in open field (OF) test (decrease in the locomotor activity, as well as in frequency and cumulative duration in the centre zone) and in elevated plus maze (EPM) test (decrease in frequency and cumulative duration in open arms, and total exploratory activity), that were accompanied with a mild decrease in the number of PV interneurons in hippocampus. Chronic exercise protocol induced significant increase in hippocampal PV neurons (dentate gyrus and CA1 region), followed by anxiolytic-like behavioral changes, observed in both OF and EPM (increase in all estimated parameters), and in evoked beam-walking test (increase in time to cross the beam), compared to ND treated animals. The applied dose of ND was sufficient to attenuate beneficial effects of exercise in rats by means of decreased exercise-induced anxiolytic effect, as well as to reverse exercise-induced augmentation in number of PV immunoreactive neurons in hippocampus. Our results implicate the possibility that alterations in hippocampal PV interneurons (i.e. GABAergic system) may be involved in modulation of anxiety level induced by ND abuse and/or extended exercise protocols.

Nandrolone decanoate appears to increase bone callus formation in young adult rats after a complete femoral fracture.

To evaluate the influence of nandrolone decanoate on fracture healing and bone quality in normal rats. Male rats were assigned to four groups (n=28/group): Control group consisting of animals without any intervention, Nandrolone decanoate (DN) group consisting of animals that received intramuscular injection of nandrolone decanoate, Fracture group consisting of animals with a fracture at the mid-diaphysis of the femur, and Fracture and nandrolone decanoate group consisting of animals with a femur fracture and treatment with nandrolone decanoate. Fractures were created at the mid-diaphysis of the right femur by a blunt trauma and internally fixed using an intramedullary steel wire. The DN was injected intramuscularly twice per week (10 mg/kg of body mass). The femurs were measured and evaluated by densitometry and mechanical resistance after animal euthanasia. The newly formed bone and collagen type I levels were quantified in the callus. The treated animals had longer femurs after 28 days. The quality of the intact bone was not significantly different between groups. The bone callus did show a larger mass in the treated rats. The administration of nandrolone decanoate did not affect the quality of the intact bone, but might have enhanced the bone callus formation.