Nandrolone Decanoate supplementation promotes AMPK activation and divergent brain connectivity rearrangements in adult and aged mice.

Abnormalities in energetic and proteic homeostasis during ageing relate to neurodegenerative diseases. The mitochondria are a hub of oxidative metabolism, influencing autophagic flux. Ageing can lead to a functional disruption of these systems, leading to neuroenergetic and proteotoxic imbalance. Lower levels of testosterone have been proposed as a mechanism accelerating functional decline during ageing. In this study we investigated whether nandrolone decanoate (ND), an analog of testosterone, in aged animals improves mitochondrial bioenergetics and autophagy. Albino CF1 mice of 3 and 18 months of age, were separated in 4 groups that received daily subcutaneous injections for 15 days of either ND (15mg/kg), or vehicle. Were performed baseline and 14th day 18FDG uptake analysis, through positron emission tomography scan. High resolution respirometry was performed to assess functionally mitochondrial respiratory states and respiratory control ratio (RCR) in synaptossomes fractions. Also, hypothalamic immunocontent of AMPK, pAMPKT172, Beclin-1 and BCL-2 LC3 was assessed. Results demonstrate that aged animals did not display alterations nor in 18FDG uptake, neither in mitochondrial respiratory states. Also, aged mice displayed reduced pAMPKT172/ AMPK ratio, and increased LC3-II compared to adult controls. Curiously, ND in aged mice did neither increase 18FDG uptake, nor alter mitochondrial states. Albeit, ND increased pAMPKT172/ AMPK ratio, LC3-II turnover, as well as increased RCR. This suggest that ageing does not culminate necessarily in bioenergetics alterations in brain, although biomarkers of energetic status and autophagy are reduced. ND improved bioenergetic efficiency and autophagy in aged mice. These benefits are probably mediated by reprogramation of AMPK signalling.

AMELIORATIVE EFFECTS OF PUNICA GRANATUMON RENAL TUBULAR NECROSIS INDUCED BY NANDROLONE DECANOATE IN MICE MODEL

Objective: To observe the effects of nandrolone decanoateon renal tubules and its protection by punicagranatum (pomegranate) in mice. Study Design: Lab based experimental study. Place and Duration of Study: One year in Anatomy department, Army Medical College, Rawalpindi, in association with National Institution of Health, Islamabad. Methodology: Forty healthy BALB/c mice of both sexes with weight range of 2 5-30gms were equally disseminated into four groups, A as control while B, C and D as trial groups. Three trial groups were inoculated Nandrolone Decanoate 1mg per 100gm of body weight, through intramuscular injections in the hind limb, once weekly for eight weeks. Pomegranate nector was administered in animals of trial group C (3ml per kg of body weight) en route oral gavage tube daily, whereas animals in trial group D was administered pomegranate peel extract (200mg per kg body weight) via oral gavage tube daily for eight weeks. Evaluation of the outcomes of trial groups B, C & D was done amongst them and with control group A. Results: In nandrolone decanoate injected experimental group B, tubular necrosis were appreciated in comparison with control group A (p˂ 0.001), and showed statistical improvement when evaluation was done with pomegranate nectar and pomegranate peel extract treated trial groups C (0.001) and D (p=0.001), correspondingly. Conclusion: Punicagranatum in two forms, as nectar and peel extract, has almost identical curative effects on steroid administered renal tubular mutilation.

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

Background During 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). Results Diameter, 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. Conclusions Nandrolone alone or combined with swimming decreased morphometric parameters and amount of AR in testicle tissue. Changes in the redox state indicate reproductive dysfunction.

Some groups of drugs which use is associated with development of drug-induced atrial fibrillation

Recently, more and more attention has been paid to the problem of drug‑induced (DI) atrial fibrillation (AF). It is known that the development of DI AF can be associated with the intake of cardiovascular and anticancer drugs, drugs that affect the central nervous system or respiratory organs. However, there are other drugs that can provoke DI AF, which practitioners are less aware of. This article is a review of the current literature on DI AF associated with the intake of other groups of drugs and individual drugs that are not included in the above groups. Analysis of the available literature has shown that the incidence of DI AF reaches 6.9% when taking zoledronic acid and 1.5% when taking alendronate, although data from different authors regarding the causal relationship between bisphosphonate therapy and the development of AF are ambiguous. The use of high doses of glucocorticosteroids (at a daily dose of ≥ 7.5 mg in terms of prednisolone) is also associated with an increased risk of AF (OR = 6.07; 95% CI: 3.90–9.42). Treatment with non‑steroidal anti‑inflammatory drugs is also associated with a higher risk of developing DI AF compared to those who do not use it – the incidence rate is 1.17 (95% CI: 1.10–1.24) for nonselective and 1.27 (95% CI: 1.20–1.34) for cyclooxygenase‑2 inhibitors. The literature contains a description of clinical cases of DI AF while taking immunosuppressants (azathioprine, methotrexate + etanercept, fingolimod, cyclosporine), drugs that affect the genitourinary system (vardenafil, sildenafil, yohimbine hydrochloride, hexoprenaline), local anesthetics, bupacaero testosterone, stanozolol, testosterone cypionate, nandrolone decanoate extraboline) and nicotine‑containing products (nicotine‑containing chewing gum).

SWIM TRAINING REVERSES SOME EFFECTS OF NANDROLONE DECANOATE IN WISTAR RATS

ABSTRACT Introduction: The indiscriminate use of androgenic steroids may have deleterious effects on human tissue. Objectives: Evaluate the effects of chronic administration of the steroid nandrolone decanoate (DECA) on autonomic cardiovascular modulation, kidney morphometry and the association between these variables in Wistar rats subjected to physical training with swimming. Methods: Thirty-two male Wistar rats aged 20 weeks were distributed among four experimental groups according to the training received: sedentary control (SC), sedentary treated with DECA (SD), trained control (TC) and trained treated with DECA (TD). The hemodynamic parameters, including blood pressure and variations in systolic blood pressure (SBPV) and diastolic blood pressure (DBPV), and kidney morphometry were evaluated. The level of significance adopted was 5%. Results: The SD group had higher baseline SBP and DBP values when compared to the SC, TC and TD groups, which were similar to each other. The rats in the SD group had higher systolic blood pressure (SBPV) and diastolic blood pressure (DBPV) variation values and higher absolute and normalized values in the LF band of the DBPV when compared to the animals in the SC, TC and TD groups. The animals in the SD group had a significantly higher rate of kidney fibrosis compared to the SC, TC and TD groups. There were no significant differences between the sympathetic modulation of SBPV through the LF component and kidney fibrosis. Conclusions: Physical training with swimming was effective in preventing the increase in blood pressure levels and lowering the occurrence of kidney fibrosis in animals treated with anabolic steroids. Level of Evidence IV; Series of cases .