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Keywords = nandrolone

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15 pages, 1010 KiB  
Systematic Review
Exogenous Versus Endogenous Nandrolone in Doping Investigations: A Systematic Literature Review
by Roberto Scendoni, Giulia Ricchezze, Gianmario Mietti, Alice Cerioni, Rino Froldi, Mariano Cingolani, Erika Buratti and Marta Cippitelli
Appl. Sci. 2024, 14(22), 10641; https://doi.org/10.3390/app142210641 - 18 Nov 2024
Viewed by 2524
Abstract
Nandrolone, or 19-nortestosterone, is an anabolic steroid derived from testosterone, known for its androgenic and anabolic effects. Often used illicitly by athletes to boost performance, its use is banned by the World Anti-Doping Agency (WADA) in and out of competition. Nandrolone’s main metabolites, [...] Read more.
Nandrolone, or 19-nortestosterone, is an anabolic steroid derived from testosterone, known for its androgenic and anabolic effects. Often used illicitly by athletes to boost performance, its use is banned by the World Anti-Doping Agency (WADA) in and out of competition. Nandrolone’s main metabolites, 19-norandrosterone (19-NA) and 19-noretiocholanolone (19-NE), are typically detected in urine. This systematic review, registered with PROSPERO and following PRISMA guidelines, examines nandrolone’s metabolism, factors affecting its natural production, and the analytical methods used in doping tests. Searches on PubMed, Scopus, and Web of Science yielded 517 studies, of which 57 were selected for analysis after excluding duplicates and unrelated articles. Descriptive statistics were applied to assess data on metabolic pathways, endogenous production influences, and detection techniques. Based on this review, it clearly emerges that the only technique that can distinguish endogenous production from an exogenous intake is gas chromatography/combustion/isotope ratio mass spectrometry (GC-C-IRMS). In addition, factors influencing endogenous production are considered and explored. Overall, this review provides useful information regarding nandrolone and its main metabolites. Full article
(This article belongs to the Special Issue Research of Sports Medicine on Health Care)
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28 pages, 3913 KiB  
Article
Abuse of Anabolic-Androgenic Steroids as a Social Phenomenon and Medical Problem—Its Potential Negative Impact on Reproductive Health Based on 50 Years of Case Report Analysis
by Monika Skrzypiec-Spring, Julia Rozmus, Gina Abu Faraj, Kinga Brawańska-Maśluch, Krzysztof Kujawa and Adam Szeląg
J. Clin. Med. 2024, 13(19), 5892; https://doi.org/10.3390/jcm13195892 - 2 Oct 2024
Cited by 1 | Viewed by 3782
Abstract
Background/Objectives: Illegal anabolic-androgenic steroids are a significant lifestyle factor in infertility. The aim of our study was to analyze clinical cases resulting from their use for their frequency, geographical location, dynamics, substances used, the age and gender of the users, and the types [...] Read more.
Background/Objectives: Illegal anabolic-androgenic steroids are a significant lifestyle factor in infertility. The aim of our study was to analyze clinical cases resulting from their use for their frequency, geographical location, dynamics, substances used, the age and gender of the users, and the types of clinical complications. Methods: Publications were obtained by searching PubMed for the following terms: ‘anabolic-androgenic steroids’ and ‘clinical case’. Publications from 1973 to 2022 were qualified for the analysis. Results: An increasing trend in the number of clinical cases resulting from the use of steroids, as well as the number of substances used simultaneously, was observed. The substances changed over the decades, but in the last 20 years, testosterone, nandrolone, stanozolol, methandienone, trenbolone, and methenolone have predominated. Cardiological side effects predominated in each period, with a continuous increase in their occurrence. The most common among these were myocardial infarctions and hypertrophic cardiomyopathy. The next most numerous adverse events involved psychiatric, endocrinological, hepatic, and oncological problems. We demonstrated a possible relationship between the use of individual steroids and medical issues; the strongest associations were between testosterone and endocrine complications, and methylstenbolone and hepatic complications. Conclusions: There has been an increasing trend in case reports describing serious health problems associated with the use of anabolic-androgenic steroids, a tendency to use several substances simultaneously, and a preferential use of substances with a high potential of causing serious side effects. These phenomena mainly concern men, with an average age of 30, and the health problems that dominate in clinical case reports—including serious cardiological, psychiatric, endocrinological, hepatic, and oncological diseases—may potentially affect reproductive health and pose a challenge for reproductive medicine. Full article
(This article belongs to the Special Issue Reproductive Endocrinology and Infertility)
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19 pages, 330 KiB  
Article
The Use of Anabolic Steroids by Bodybuilders in the State of Sergipe, Brazil
by Josué Cruz dos Santos, Erivaldo de Souza, Daniela Meneses-Santos, Carla Roberta de Oliveira Carvalho, Jymmys Lopes dos Santos, Felipe J. Aidar and Anderson Carlos Marçal
Eur. J. Investig. Health Psychol. Educ. 2024, 14(5), 1451-1469; https://doi.org/10.3390/ejihpe14050096 - 16 May 2024
Cited by 1 | Viewed by 4610
Abstract
Bodybuilding, as a high-performance sport, requires regular strength and resistance exercises with the principal objective of increasing muscle hypertrophy. However, many bodybuilders resort to the use of anabolic-androgenic steroids (AASs) to improve their performance in a short period of time. This study employs [...] Read more.
Bodybuilding, as a high-performance sport, requires regular strength and resistance exercises with the principal objective of increasing muscle hypertrophy. However, many bodybuilders resort to the use of anabolic-androgenic steroids (AASs) to improve their performance in a short period of time. This study employs a survey-type, cross-sectional, descriptive–analytical method to evaluate the profile of bodybuilding athletes in the State of Sergipe, Brazil, and verify the level of knowledge/awareness about the health risks and impacts resulting from the use of such substances. Finite- and convenience-type populations are assessed, including individuals of both sexes, aged older than 18 years, self-declared bodybuilding athletes residing in the State of Sergipe, Brazil, and participating in regional and/or state competitions. As a result, no significant relationships were determined between sex (p = 0.492), age (p = 0.460), family income (p = 0.141), and medical follow-up sessions. For the variables level of education and medical follow-up vs. no follow-up sessions, a significant result was achieved (p = 0.01), with 74.3% of individuals reporting having follow-up treatment and 25.7% responding that they had no follow-up treatment, a percentage representing the group that completed their higher education. The substances most used by the athletes were Sustanon 250 or Durateston, Nandrolone Decanoate (Deca or Deca-Durabolin), and Testosterone. The most-reported acute side effects were acne at 33.8% (n = 20), irritability at 32.1% (n = 19), alopecia (hair loss), and nervousness at 23.7% (n = 14). The most-reported chronic side effects were arterial hypertension at 36.0% (n = 9), liver disease at 28.0% (n = 7), and cancer (non-specific) at 8.0% (n = 2). We concluded that, regardless of the athletes’ socioeconomic profiles, the use of AASs was high, with two or more substances being used in combination and for a prolonged period. Thus, it is necessary to promote awareness campaigns regarding the use of AASs and their effects on high-performance and recreational athletes. Full article
21 pages, 3311 KiB  
Article
Anabolic Steroids Activate the NF-κB Pathway in Porcine Ovarian Putative Stem Cells Independently of the ZIP-9 Receptor
by Kamil Wartalski, Jerzy Wiater, Patrycja Maciak, Agnieszka Pastuła, Grzegorz J. Lis, Marcin Samiec, Monika Trzcińska and Małgorzata Duda
Int. J. Mol. Sci. 2024, 25(5), 2833; https://doi.org/10.3390/ijms25052833 - 29 Feb 2024
Cited by 8 | Viewed by 2037
Abstract
Boldenone (Bdn) and nandrolone (Ndn) are anabolic androgenic steroids (AASs) that, as our previous studies have shown, may increase the risk of neoplastic transformation of porcine ovarian putative stem cells (poPSCs). The NF-κB pathway may be important in the processes of carcinogenesis and [...] Read more.
Boldenone (Bdn) and nandrolone (Ndn) are anabolic androgenic steroids (AASs) that, as our previous studies have shown, may increase the risk of neoplastic transformation of porcine ovarian putative stem cells (poPSCs). The NF-κB pathway may be important in the processes of carcinogenesis and tumour progression. Therefore, in this work, we decided to test the hypothesis of whether Bdn and Ndn can activate the NF-κB pathway by acting through the membrane androgen receptor ZIP-9. For this purpose, the expression profiles of both genes involved in the NF-κB pathway and the gene coding for the ZIP-9 receptor were checked. The expression and localization of proteins of this pathway in poPSCs were also examined. Additionally, the expression of the ZIP-9 receptor and the concentration of the NF-κB1 and 2 protein complex were determined. Activation of the NF-κB pathway was primarily confirmed by an increase in the relative abundances of phosphorylated forms of RelA protein and IκBα inhibitor. Reduced quantitative profiles pinpointed not only for genes representing this pathway but also for unphosphorylated proteins, and, simultaneously, decreased concentration of the NF-κB1 and 2 complex may indicate post-activation silencing by negative feedback. However, the remarkably and sustainably diminished expression levels noticed for the SLC39A9 gene and ZIP-9 protein suggest that this receptor does not play an important role in the regulation of the NF-κB pathway. Full article
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19 pages, 14141 KiB  
Article
RNAseq Analysis of Livers from Pigs Treated with Testosterone and Nandrolone Esters: Selection and Field Validation of Transcriptional Biomarkers
by Alessandro Benedetto, Kamil Šťastný, Nunzia Giaccio, Marianna Marturella, Elena Biasibetti, Maddalena Arigoni, Raffaele Calogero, Marilena Gili, Marzia Pezzolato, Kristína Tošnerová, Nikola Hodkovicová, Martin Faldyna, Roberto Puleio, Giancarlo Bozzo and Elena Bozzetta
Animals 2023, 13(22), 3495; https://doi.org/10.3390/ani13223495 - 13 Nov 2023
Cited by 2 | Viewed by 1630
Abstract
The use of anabolic–androgenic steroids (AASs) as growth promoters in farm animals is banned in the European Union, representing both an illicit practice and a risk for consumer health. However, these compounds are still illegally administered, often in the form of synthetic esters. [...] Read more.
The use of anabolic–androgenic steroids (AASs) as growth promoters in farm animals is banned in the European Union, representing both an illicit practice and a risk for consumer health. However, these compounds are still illegally administered, often in the form of synthetic esters. This work aimed to characterize significant coding RNA perturbations related to the illicit administration of testosterone and nandrolone esters in fattening pigs. A total of 27 clinically healthy 90-day-old pigs were randomly assigned to test and control groups. Nine animals were treated with testosterone esters (Sustanon®) and other nine with nandrolone esters (Myodine®). At the end of the trial, liver samples were collected and analyzed using RNAseq, allowing the identification of 491 differentially expressed genes (DEGs). The transcriptional signature was further characterized by a smaller sub-cluster of 143 DEGs, from which a selection of 16 genes was made. The qPCR analysis confirmed that the identified cluster could still give good discrimination between untreated gilt and barrows compared to the relative testosterone-treated counterparts. A conclusive field survey on 67 liver samples collected from pigs of different breeds and weight categories confirmed, in agreement with testosterone residue profiles, the specificity of selected transcriptional biomarkers, showing their potential applications for screening purposes when AAS treatment is suspected, allowing to focus further investigations of competent authorities and confirmatory analysis where needed. Full article
(This article belongs to the Section Pigs)
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16 pages, 2741 KiB  
Article
Effects of Nandrolone Decanoate on Skeletal Muscle and Neuromuscular Junction of Sedentary and Exercised Rats
by Felipe Cantore Tibúrcio, Ana Paula Silveira Leite, Kevin Silva Muller, Carina Guidi Pinto, Erick Valentino, Paula Aiello Tomé de Souza Castro, Cintia Yuri Matsumura, Shelly Favorito de Carvalho and Selma Maria Michelin Matheus
Medicina 2023, 59(11), 1940; https://doi.org/10.3390/medicina59111940 - 1 Nov 2023
Cited by 4 | Viewed by 5037
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Section Sports Medicine and Sports Traumatology)
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14 pages, 2978 KiB  
Article
Crystal Structure and Intermolecular Energy for Some Nandrolone Esters
by Liviu Mare, Marieta Muresan-Pop, Pompilia Mioara Purcea Lopes, Alexandru Turza, Gheorghe Borodi and Violeta Popescu
Molecules 2023, 28(20), 7179; https://doi.org/10.3390/molecules28207179 - 19 Oct 2023
Cited by 1 | Viewed by 2439
Abstract
Nandrolone (Estr-4-en-17β-ol-3-one) is a derivative of testosterone and a naturally occurring anabolic–androgenic agent which belongs to the steroid group. Crystal structures of four short, medium and long esterified forms of nandrolone, including propionate, phenylpropionate, cypionate and undecanoate were determined using single-crystal X-ray diffraction. [...] Read more.
Nandrolone (Estr-4-en-17β-ol-3-one) is a derivative of testosterone and a naturally occurring anabolic–androgenic agent which belongs to the steroid group. Crystal structures of four short, medium and long esterified forms of nandrolone, including propionate, phenylpropionate, cypionate and undecanoate were determined using single-crystal X-ray diffraction. Crystal packing, supramolecular features and intermolecular interactions were described based on a quantitative and qualitative Hirshfeld surfaces analysis accompanied by evaluation of crystal energies and intermolecular interactions computation. Also, the solubility of the esters was investigated from a pharmaceutical perspective. Full article
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14 pages, 2691 KiB  
Article
Structural Changes in the Skeletal Muscle of Pigs after Long-Term Administration of Testosterone, Nandrolone and a Combination of the Two
by Kristýna Skoupá, Andrej Bátik, Kamil Št’astný and Zbyšek Sládek
Animals 2023, 13(13), 2141; https://doi.org/10.3390/ani13132141 - 28 Jun 2023
Cited by 4 | Viewed by 2891
Abstract
Anabolic steroid hormones (AASs) are used in most countries of the world to accelerate the growth of animals, increase the volume of their muscles and thereby increase meat production. However, there is a strict ban on the use of AASs in the fattening [...] Read more.
Anabolic steroid hormones (AASs) are used in most countries of the world to accelerate the growth of animals, increase the volume of their muscles and thereby increase meat production. However, there is a strict ban on the use of AASs in the fattening of all animals in all countries of the European Union, and there must therefore be effective methods of detection and control of these substances. Methods based on chromatography and mass spectrometry may no longer be completely effective when faced with new synthetic steroids of unknown chemical structures and low concentrations. Therefore, there is an effort to develop new methods of AAS detection, based primarily on the monitoring of biological changes at the level of gene expression or changes in metabolism or structure at the cellular level. More detailed knowledge of the mechanisms of action of AASs on tissues is essential for these methods, and histological changes are one of them. In this study, we report histological changes in muscle structure after AAS application, specifically in the size of muscle fibers, the amount of endomysium and the number of nuclei and satellite cells in muscle fibers. A pig model was also intentionally used for the study, as no such study has been carried out on this species, and at the same time, pork is one of the most consumed meats across Europe. The results of histology and fluorescent antibody labeling showed that AASs increased the diameter and surface area of muscle fibers and also significantly increased the number of satellite cells on the fiber surface. The evident correlations between the number of satellite cells, all nuclei and the diameters of muscle fibers between some experimental groups provide evidence that the selected histological parameters could be additional detection mechanisms for screening a large number of samples and indicate the possibility of the presence of AASs in pork meat in the future. Full article
(This article belongs to the Section Pigs)
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18 pages, 2184 KiB  
Article
Nandrolone Decanoate and Swimming Affects Cardiodynamic and Morphometric Parameters in the Isolated Rat Heart
by Jasmina Sretenovic, Vladimir Zivkovic, Ivan Srejovic, Suzana Pantovic, Jovana Joksimovic Jovic, Maja Nikolic, Tamara Nikolic Turnic, Maja Savic, Maja Jevdjevic, Zoran Milosavljevic, Sergej Bolevich and Vladimir Jakovljevic
Life 2022, 12(8), 1242; https://doi.org/10.3390/life12081242 - 16 Aug 2022
Cited by 7 | Viewed by 4303
Abstract
(1) Background: The aim of this study was to show the effects of swimming and nandrolone administration on cardiodynamic and morphometric parameters of the isolated rat heart. (2) The study included 72 Wistar rats, divided into three groups, scheduled to be sacrificed after [...] Read more.
(1) Background: The aim of this study was to show the effects of swimming and nandrolone administration on cardiodynamic and morphometric parameters of the isolated rat heart. (2) The study included 72 Wistar rats, divided into three groups, scheduled to be sacrificed after the second, third, and fourth week. Each group was divided into four subgroups: control (T-N-), nandrolone (T-N+), swimming training (T+N-), and swimming training plus nandrolone (T+N+) group. The rats from T+N- and T+N+ swam 1 h/day, 5 days/week while ones from T-N+ and T+N+ received weekly nandrolone decanoate (20 mg/kg). The isolated hearts were perfused according to the Langendorff technique and measured parameters: dp/dt max/min, SLVP, DLVP, heart rate, and coronary flow. Hearts were fixed and stained with H/E and Masson trichrome dyes. (3) dp/dt max and dp/dt min were increased in the T-N+ group at higher perfusion pressure compared to the T-N- group. SLVP and DLVP were increased in all groups after the 4th week. Collagen content was increased in T-N+ by 403% and in T+N+ by 357% groups, while it was decreased in T+N- compared to the control after 4th week. (4) Conclusions: Nandrolone alone or combined with swimming had a deleterious effect on myocardial function and perfusion. Full article
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41 pages, 3457 KiB  
Systematic Review
The Effect of Non-Pharmacological and Pharmacological Interventions on Measures Associated with Sarcopenia in End-Stage Kidney Disease: A Systematic Review and Meta-Analysis
by Daniel S. March, Thomas J. Wilkinson, Thomas Burnell, Roseanne E. Billany, Katherine Jackson, Luke A. Baker, Amal Thomas, Katherine A. Robinson, Emma L. Watson, Matthew P. M. Graham-Brown, Arwel W. Jones and James O. Burton
Nutrients 2022, 14(9), 1817; https://doi.org/10.3390/nu14091817 - 27 Apr 2022
Cited by 20 | Viewed by 5172
Abstract
This systematic review and meta-analysis provides a synthesis of the available evidence for the effects of interventions on outcome measures associated with sarcopenia in end-stage kidney disease (ESKD). Thirteen databases were searched, supplemented with internet and hand searching. Randomised controlled trials of non-pharmacological [...] Read more.
This systematic review and meta-analysis provides a synthesis of the available evidence for the effects of interventions on outcome measures associated with sarcopenia in end-stage kidney disease (ESKD). Thirteen databases were searched, supplemented with internet and hand searching. Randomised controlled trials of non-pharmacological or pharmacological interventions in adults with ESKD were eligible. Trials were restricted to those which had reported measures of sarcopenia. Primary outcome measures were hand grip strength and sit-to-stand tests. Sixty-four trials were eligible (with nineteen being included in meta-analyses). Synthesised data indicated that intradialytic exercise increased hand grip strength (standardised mean difference, 0.58; 0.24 to 0.91; p = 0.0007; I2 = 40%), and sit-to-stand (STS) 60 score (mean difference, 3.74 repetitions; 2.35 to 5.14; p < 0.001; I2 = 0%). Intradialytic exercise alone, and protein supplementation alone, resulted in no statistically significant change in STS5 (−0.78 s; −1.86 to 0.30; p = 0.16; I2 = 0%), and STS30 (MD, 0.97 repetitions; −0.16 to 2.10; p = 0.09; I2 = 0%) performance, respectively. For secondary outcomes, L-carnitine and nandrolone-decanoate resulted in significant increases in muscle quantity in the dialysis population. Intradialytic exercise modifies measures of sarcopenia in the haemodialysis population; however, the majority of trials were low in quality. There is limited evidence for efficacious interventions in the peritoneal dialysis and transplant recipient populations. Full article
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13 pages, 3924 KiB  
Article
Sources, Pollution Characteristics, and Ecological Risk Assessment of Steroids in Beihai Bay, Guangxi
by Chaoxing Ren, Xiao Tan, Cuimei Huang, Hui Zhao and Wenlu Lan
Water 2022, 14(9), 1399; https://doi.org/10.3390/w14091399 - 27 Apr 2022
Cited by 18 | Viewed by 2898
Abstract
Steroids are environmental endocrine disruptors that are discharged from vertebrates and are also byproducts of aquaculture. They have strong endocrine disrupting effects and are extremely harmful to the environment. The pollution of steroids in Beihai Bay was assessed through analyzing sources from rivers [...] Read more.
Steroids are environmental endocrine disruptors that are discharged from vertebrates and are also byproducts of aquaculture. They have strong endocrine disrupting effects and are extremely harmful to the environment. The pollution of steroids in Beihai Bay was assessed through analyzing sources from rivers entering the bay. Six different types of steroids were detected in seagoing rivers, seagoing discharge outlets, and marine aquaculture farms, ranging from 0.12 (methyltestosterone) to 2.88 ng/L (estrone), from 0.11 (cortisol) to 5.41 ng/L (6a-methylprednisone (Dragon)), and from 0.13 (estradiol) to 2.51 ng/L (nandrolone), respectively. Moreover, 5 steroids were detected in 13 of the 19 seawater monitoring stations, accounting for 68.4% of the samples, and their concentrations ranged from 0.18 (methyltestosterone) to 4.04 ng/L (estrone). Furthermore, 7 steroids were detected in 15 of the 19 sediment monitoring stations, accounting for 78.9% of the samples, with concentrations ranging from 26 (estrone) to 776 ng/kg(androsterone). Thus, the main source of marine steroids were the discharging rivers and pollution sources entering the sea. An ecological risk assessment indicated that estrone and methyltestosterone were at high risk in this region; 17β estradiol (E2β) was medium risk, and other steroids were of low or no risk. This study provides a scientific basis for ecological risk assessment and control. Full article
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36 pages, 4562 KiB  
Article
The Molecular Quality and Mitochondrial Activity of Porcine Cumulus–Oocyte Complexes Are Affected by Their Exposure to Three Endocrine-Active Compounds under 3D In Vitro Maturation Conditions
by Gabriela Gorczyca, Kamil Wartalski, Marek Romek, Marcin Samiec and Małgorzata Duda
Int. J. Mol. Sci. 2022, 23(9), 4572; https://doi.org/10.3390/ijms23094572 - 20 Apr 2022
Cited by 31 | Viewed by 4486
Abstract
Thus far, the potential short- and long-term detrimental effects of a variety of environmental chemicals designated as endocrine-active compounds (EACs) have been found to interfere with histo- and anatomo-physiological functions of the reproductive system in humans and wildlife species. For those reasons, this [...] Read more.
Thus far, the potential short- and long-term detrimental effects of a variety of environmental chemicals designated as endocrine-active compounds (EACs) have been found to interfere with histo- and anatomo-physiological functions of the reproductive system in humans and wildlife species. For those reasons, this study sought to examine whether selected EACs, which encompass the fungicide vinclozolin (Vnz), the androgenic anabolic steroid nandrolone (Ndn) and the immunosuppressant cyclosporin A (CsA), affect the developmental competence and molecular quality (MQ) of porcine cumulus–oocyte complexes (COCs) subjected to in vitro maturation (IVM) under 3D culture conditions. The COCs underwent 3D-IVM in the presence of Vnz, Ndn or CsA for 48 h. To explore whether the selected EACs induce internucleosomal DNA fragmentation in cumulus cells (CCs), TUNEL-assisted detection of late apoptotic cells was performed. Additionally, for the detailed evaluation of pro- and antiapoptotic pathways in COCs, apoptosis proteome profiler arrays were used. To determine changes in intracellular metabolism in COCs, comprehensive assessments of mitochondrial ultrastructure and activity were carried out. Moreover, the relative abundances (RAs) of mRNAs transcribed from genes that are involved in scavenging reactive oxygen species (ROS), such as SIRT3 and FOXO3, and intramitochondrial bioenergetic balance, such as ATP synthase subunit (ATP5A1), were ascertained. Finally, to investigate the extent of progression of oocyte maturation, the intraooplasmic levels of cAMP and the RAs of mRNA transcripts encoding regulatory and biocatalytic subunits of a heterodimeric meiosis-promoting factor, termed cyclin B1 (CCNB1) and cyclin-dependent kinase 1 (CDC2), were also estimated. The obtained results provide, for the first time, strong evidence that both Vnz and Ndn decrease the developmental competence of oocytes and stimulate apoptosis processes in CCs. The present study is also the first to highlight that Vnz accelerates the maturation process in immature oocytes due to both increased ROS production and the augmented RA of the CCNB1 gene. Furthermore, Vnz was proven to trigger proapoptotic events in CCs by prompting the activity of the FOXO3 transcription factor, which regulates the mitochondrial apoptosis pathway. In turn, Ndn was shown to inhibit oocyte maturation by inducing molecular events that ultimately lead to an increase in the intraooplasmic cAMP concentration. However, due to the simultaneous enhancement of the expression of TNF-β and HSP27 proteins in CCs, Ndn might be responsible for the onset of their neoplastic transformation. Finally, our current investigation is the first to clearly demonstrate that although CsA did not interfere with the nuclear and cytoplasmic maturation of oocytes, by inducing mitophagy in CCs, it disrupted oocyte metabolism, consequently attenuating the parameters related to the MQ of COCs. Summing up, Vnz, Ndn and CsA reduced not only the processes of growth and IVM but also the MQ of porcine COCs, which might make them unsuitable for assisted reproductive technologies (ARTs) such as in vitro fertilization by either gamete co-incubation or intracytoplasmic sperm injection (ICSI) and cloning by somatic cell nuclear transfer (SCNT). Full article
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23 pages, 2508 KiB  
Article
Anabolic Steroids-Driven Regulation of Porcine Ovarian Putative Stem Cells Favors the Onset of Their Neoplastic Transformation
by Gabriela Gorczyca, Kamil Wartalski, Jerzy Wiater, Marcin Samiec, Zbigniew Tabarowski and Małgorzata Duda
Int. J. Mol. Sci. 2021, 22(21), 11800; https://doi.org/10.3390/ijms222111800 - 30 Oct 2021
Cited by 31 | Viewed by 3567
Abstract
Nandrolone (Ndn) and boldenone (Bdn), the synthetic testosterone analogues with strong anabolic effects, despite being recognized as potentially carcinogenic compounds, are commonly abused by athletes and bodybuilders, which includes women, worldwide. This study tested the hypothesis that different doses of Ndn and Bdn [...] Read more.
Nandrolone (Ndn) and boldenone (Bdn), the synthetic testosterone analogues with strong anabolic effects, despite being recognized as potentially carcinogenic compounds, are commonly abused by athletes and bodybuilders, which includes women, worldwide. This study tested the hypothesis that different doses of Ndn and Bdn can initiate neoplastic transformation of porcine ovarian putative stem cells (poPSCs). Immunomagnetically isolated poPSCs were expanded ex vivo in the presence of Ndn or Bdn, for 7 and 14 days. Results show that pharmacological doses of both Ndn and Bdn, already after 7 days of poPSCs culture, caused a significant increase of selected, stemness-related markers of cancer cells: CD44 and CD133. Notably, Ndn also negatively affected poPSCs growth not only by suppressing their proliferation and mitochondrial respiration but also by inducing apoptosis. This observation shows, for the first time, that chronic exposure to Ndn or Bdn represents a precondition that might enhance risk of poPSCs neoplastic transformation. These studies carried out to accomplish detailed molecular characterization of the ex vivo expanded poPSCs and their potentially cancerous derivatives (PCDs) might be helpful to determine their suitability as nuclear donor cells (NDCs) for further investigations focused on cloning by somatic cell nuclear transfer (SCNT). Such investigations might also be indispensable to estimate the capabilities of nuclear genomes inherited from poPSCs and their PCDs to be epigenetically reprogrammed (dedifferentiated) in cloned pig embryos generated by SCNT. This might open up new possibilities for biomedical research aimed at more comprehensively recognizing genetic and epigenetic mechanisms underlying not only tumorigenesis but also reversal/retardation of pro-tumorigenic intracellular events. Full article
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10 pages, 1997 KiB  
Article
The Impact of Nandrolone Decanoate in the Osseointegration of Dental Implants in a Rabbit Model: Histological and Micro-Radiographic Results
by Saturnino Marco Lupi, Alessandra Nicole Sassi, Alessandro Addis and Ruggero Rodriguez y Baena
Materials 2021, 14(9), 2258; https://doi.org/10.3390/ma14092258 - 27 Apr 2021
Cited by 1 | Viewed by 3277
Abstract
Despite high rates of osseointegration in healthy patients, complex cases present an increased risk of osseointegration failure when treated with dental implants. Furthermore, if immediate loading of the implants is used, maximizing the response of the host organism would be desirable. Anabolic steroids, [...] Read more.
Despite high rates of osseointegration in healthy patients, complex cases present an increased risk of osseointegration failure when treated with dental implants. Furthermore, if immediate loading of the implants is used, maximizing the response of the host organism would be desirable. Anabolic steroids, such as Nandrolone Decanoate (ND), are reported to have beneficial clinical effects on various bone issues such as osteoporosis and bone fractures. However, their beneficial effects in promoting osseointegration in dental implant placement have not been documented. The study aimed to examine histological changes induced by ND in experimental dental implants in rabbit models. Two dental implants were placed in the tibias of 24 adult rabbits. Rabbits were allocated to one of two groups: control group or test group. Rabbits in the latter group were given nandrolone decanoate (15 mg/kg, immediately after implant placement and after 1 week). Micro-radiographic and histological analyses were assessed to characterize the morphological changes promoted by the nandrolone decanoate use. Total bone volume and fluorescence were significantly higher in the control group after 2 weeks. Such a difference between the two groups might indicate that, initially, nandrolone lengthens the non-specific healing period characteristic of all bone surgeries. However, after the beginning of the reparative processes, the quantity of newly formed bone appears to be significantly higher, indicating a positive stimulation of the androgen molecule on bone metabolism. Based on micro-radiology and fluorescence microscopy, nandrolone decanoate influenced bone regeneration in the implant site. The anabolic steroid nandrolone decanoate affects the healing processes of the peri-implant bone and therefore has the potential to improve the outcomes of implant treatment in medically complex patients. Full article
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24 pages, 3909 KiB  
Review
Nandrolone Decanoate: Use, Abuse and Side Effects
by Federico Giuseppe Patanè, Aldo Liberto, Andreana Nicoletta Maria Maglitto, Pasquale Malandrino, Massimiliano Esposito, Francesco Amico, Giuseppe Cocimano, Giuseppe Li Rosi, Dario Condorelli, Nunzio Di Nunno and Angelo Montana
Medicina 2020, 56(11), 606; https://doi.org/10.3390/medicina56110606 - 11 Nov 2020
Cited by 65 | Viewed by 22787
Abstract
Background and Objectives: Androgens play a significant role in the development of male reproductive organs. The clinical use of synthetic testosterone derivatives, such as nandrolone, is focused on maximizing the anabolic effects and minimizing the androgenic ones. Class II anabolic androgenic steroids (AAS), [...] Read more.
Background and Objectives: Androgens play a significant role in the development of male reproductive organs. The clinical use of synthetic testosterone derivatives, such as nandrolone, is focused on maximizing the anabolic effects and minimizing the androgenic ones. Class II anabolic androgenic steroids (AAS), including nandrolone, are rapidly becoming a widespread group of drugs used both clinically and illicitly. The illicit use of AAS is diffused among adolescent and bodybuilders because of their anabolic proprieties and their capacity to increase tolerance to exercise. This systematic review aims to focus on side effects related to illicit AAS abuse, evaluating the scientific literature in order to underline the most frequent side effects on AAS abusers’ bodies. Materials and Methods: A systematic review of the scientific literature was performed using the PubMed database and the keywords “nandrolone decanoate”. The inclusion criteria for articles or abstracts were English language and the presence of the following words: “abuse” or “adverse effects”. After applying the exclusion and inclusion criteria, from a total of 766 articles, only 148 were considered eligible for the study. Results: The most reported adverse effects (found in more than 5% of the studies) were endocrine effects (18 studies, 42%), such as virilization, gynecomastia, hormonal disorders, dyslipidemia, genital alterations, and infertility; cardiovascular dysfunctions (six studies, 14%) such as vascular damage, coagulation disorders, and arteriosus hypertension; skin disorders (five studies, 12%) such as pricking, acne, and skin spots; psychiatric and mood disorders (four studies, 9%) such as aggressiveness, sleep disorders and anxiety; musculoskeletal disorders (two studies, 5%), excretory disorders (two studies, 5%), and gastrointestinal disorders (two studies, 5%). Conclusions: Based on the result of our study, the most common adverse effects secondary to the abuse of nandrolone decanoate (ND) involve the endocrine, cardiovascular, skin, and psychiatric systems. These data could prove useful to healthcare professionals in both sports and clinical settings. Full article
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