Volume 4, Issue 1, June 2018, Page: 1-14
Effect of Anabolic Steroids on the Cardiac and Skeletal Muscles of Adult Male Rats
Hanan Abd-Elhakem Elgendy, Anatomy and Embryology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
Adel Abd-Elmohdy Alhawary, Anatomy and Embryology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
Mona Abd-Elrahim El-Shahat, Anatomy and Embryology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
Afaf Taha Ali, Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
Received: Nov. 28, 2017;       Accepted: Dec. 8, 2017;       Published: Feb. 7, 2018
DOI: 10.11648/j.ijcda.20180401.11      View  1228      Downloads  123
Abstract
Abuse of anabolic androgenic steroids (AASs) by athletes has been increased rapidly in many countries to improve their physical fitness and appearance. The abuses of AASs have been associated with impacts on different systems of the body. The present study was conducted to evaluate the histological changes that occurred in skeletal and cardiac muscles during nandrolone (one of AASs) treatment histologically and immunohistochmically. Forty adult male albino rats were divided into four groups. Group 1; control group, group 2; was treated with nandrolone 5 mg/kg intramuscularly weekly, group 3 was treated with nandrolone10 mg/kg intramuscularly weekly and group 4; was treated with nandrolone 20 mg/kg intramuscularly weekly. All groups were treated for 8 weeks. The specimens from the cardiac and skeletal muscles were processed for histological study using light and electron microscopes and immunohistochemical stain for detection of activated caspase-3 as an indicator for apoptotic changes. The skeletal and cardiac muscles appeared hypertrophied after nandrolone treatment. Lesions ranged from mild to severe muscular changes were also detected depending on the dose. The changes were in the form of variations of fibers size and splitting of some fibers in skeletal muscle as well as myofiber lysis, cellular infiltration, vacuolation, swelling and mitochondrial damage in both skeletal and cardiac muscles. The nuclei appeared hyperchromatic with peripherally clumped chromatin. Expression of caspase-3 was significantly increased in skeletal and cardiac tissues treated with higher doses of nandrolone. It is concluded that nandrolone injection in male albino rats induced hypertrophy and degenerative changes in the skeletal and cardiac muscles which may lead to loss of their functions.
Keywords
Nandrolone, Skeletal and Cardiac Muscles, Caspase-3, Electron Microscopy
To cite this article
Hanan Abd-Elhakem Elgendy, Adel Abd-Elmohdy Alhawary, Mona Abd-Elrahim El-Shahat, Afaf Taha Ali, Effect of Anabolic Steroids on the Cardiac and Skeletal Muscles of Adult Male Rats, International Journal of Clinical and Developmental Anatomy. Vol. 4, No. 1, 2018, pp. 1-14. doi: 10.11648/j.ijcda.20180401.11
Copyright
Copyright © 2018 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Reference
[1]
Lee DM, Mina T, Choi I, Cheon YP, Chun T, Park C S, Lee KH. Feeding Effect of an Anabolic Steroid, Nandrolone, on the Male Rat Testis. Asian-Aust J Anim Sci. 2010; 23 (12): 1566-1577.
[2]
Salas-Ramirez K Y, Montalto PR, Sisk CL. Anabolic androgenic steroids differentially affect social behaviors in adolescent and adult male Syrian hamsters. Horm Behav. 2008; 53: 378-385.
[3]
Kicman AT. Pharmacology of anabolic steroids. Br J Pharmacol. 2008; 154 (3): 502–521.
[4]
Oberlander JG, Porter DM, Penatti CA, Henderson LP. Anabolic androgenic steroid abuse: multiple mechanisms of regulation of GABAergic synapses in neuroendocrine control regions of the rodent forebrain. J Neuroendocrinol. 2012; 24 (1): 202-214.
[5]
Powers M. Performance-Enhancing Drugs. Principles of Pharmacology for Athletic Trainers, Houglum J, Harrelson GL, eds. (2nd ed.). SLACK Incorporated. 2011; P: 345.
[6]
Sjöqvist F, Garle M, Rane A. Use of doping agents, in particular anabolic steroids, in sports and society. Lancet. 2008; 371 (9627): 1872–1882.
[7]
Saha B, Rajadhyaksha GC, Ray SK. Beneficial effects of nandrolone decanoate in wasting associated with HIV. J Indian Med Assoc. 2009; 107 (5): 295–299.
[8]
Narayanan R, Mohler ML, Bohl CE, et al. Selective androgen receptor modulators in preclinical and clinical development. Nucl Recept Signal 2008; 6: e010.
[9]
Zhang X, Sui Z. Deciphering the selective androgen receptor modulators paradigm. Expert Opin Drug Discov. 2013; 8: 191–218.
[10]
Fitch KD. Androgenic-anabolic steroids and the Olympic Games. Asian J Androl. 2008; 10 (3): 384–390.
[11]
Pope HG Jr, Khalsa JH, Bhasin S. Body Image Disorders and Abuse of Anabolic-Androgenic Steroids Among Men. JAMA. 2017; 3; 317 (1): 23-24.
[12]
Du Toit E F, Rossouw E, Van Rooyen J, Lochner A. Proposed mechanisms for the anabolic steroid-induced increase in myocardial susceptibility to ischaemia/reperfusion injury. Cardiovasc J S Afr. 2005; 16: 21–28.
[13]
Crisostomo PR, Wang M, Wairiuko GM, Morrell ED, Meldrum DR. Brief exposure to exogenous testosterone increases death signaling and adversely affects myocardial function after ischemia. Am J Physiol Regul Integr Comp Physiol. 2006; 290: R1168-R1174.
[14]
Franquni JV, do Nascimento AM, de Lima EM, et al. Nandrolone decanoate determines cardiac remodeling and injury by an imbalance in cardiac inflammatory cytokines and ACE activity, blunting of the Bezold-Jarisch reflex, resulting in the development of hypertension. Steroids. 2013; 78 (3): 379–385.
[15]
Papamitsou T, Barlagiannis D, Papaliagkas V, Kotanidou E, Dermentzopoulou-Theodoridou M. Testosterone-induced hypertrophy, fibrosis and apoptosis of cardiac cells--an ultrastructural and immunohistochemicalstudy. Med Sci Monit. 2011; 17 (9): BR266-273.
[16]
Lopes RA, Neves KB, Pestana CR, et al. Testosterone induces apoptosis in vascular smooth muscle cells via extrinsic apoptotic pathway with mitochondria mitochondria-generated reactive oxygen species involvement. Am J Physiol Heart Circ Physiol. 2014; 306 (11): H1485-H1494.
[17]
Fanton L, Belhani D, Vaillant F, et al. Heart lesions associated with anabolic steroid abuse: Comparison of post-mortem findings in ath­letes and norethandrolone-induced lesions in rabbits. Exp Toxicol Pathol. 2009; 61 (4): 317–323.
[18]
Saffitz, J E. The hear, Ch: 11 in Essential Pathology, Rubin E. (editor), 6th ed. Lippincott Wiliams& Wilkins. 2014; P: 281–316.
[19]
Bancroft JD, Layton C. The Hematoxylins and Eosin, Ch: 10 In: Theory and Practice of histological techniques, 7th edition, (eds S. K. Suvarna, C. Layton, J. D. Bancroft), London: Churchill Livingstone, 2012; P: 173–214.
[20]
Jackson P, Blythe D. Immunohistochemical techniques, Ch 18 In: Theory and Practice of histological techniques, 7th edition, (eds S. K. Suvarna, C. Layton, J. D. Bancroft), London: Churchill Livingstone, 2012; P: 381-426.
[21]
John K. Electron Microscopy Methods and Protocols, methods in molecular biology, 3rd edition, Springer, New York, 2014.
[22]
Hildebrandt T. Abuse of performance-enhancing drugs. Ch 96; in Pfaff DW. (editor) Neuroscience in the 21st Century from Basic to Clinical. New York, Springer New York. 2013; P: 2813-2832.
[23]
Bisschop A, Gayan-Ramirez G, Rollier H, et al. Effects of nandrolone decanoate on respiratory and peripheral muscles in male and female rats. J Appl Physio. 1997; 82: 1112-1118.
[24]
Fontana K, Campos GER, Staron RS, da Cruz-Höfling MA. Effects of Anabolic Steroids and High-Intensity Aerobic Exercise on Skeletal Muscle of Transgenic Mice. PLoS ONE. 2013; 8 (11): e80909.
[25]
Carson JA, Lee WJ, McClung J, Hand G A. Steroid receptor concentration in aged rat hindlimb muscle: effect of anabolic steroid administration. J Appl Physiol. 2002; 93: 242-250.
[26]
Foletto MP, Ferrari F, Pere SB, de Morae SMF, Segatelli TM, Mareze-da-Costa CE. Effects of anabolic steroid treatment associated with physical training in adipose tissue of male Wistar rats. Acta Scientiarum Health Sciences. 2015; 37: 19-24.
[27]
Dela Cruz C, Agati Leandro B, Pereira Oduvaldo C. M. Effects of Nandrolone Decanoate and Resistance Exercise on Skeletal Muscle in Adult Male Rats. Int. J. Morphol. 2012; 30 (2): 613-620.
[28]
Do Nascimento AM, Lima EM, Brasil GA, et al. Serca2a and Na (+)/Ca (2+) exchanger are involved in left ventricular function following cardiac remodelling of female rats treated with anabolic androgenic steroid. Toxicol Appl Pharmacol. 2016; 15 (301): 22-30.
[29]
Diel P, Friedel A, Geyer H, et al. The prohormone 19-norandrostenedione displays selective androgen receptor modulator (SARM) like properties after subcutaneous administration. Toxicol Lett. 2008; 177 (3): 198-204.
[30]
Sinha-Hikim I, Taylor WE, Gonzalez-Cadavid NF, Zheng W, Bhasin S. Androgen receptor in human skeletal muscle and cultured muscle satellite cells: up-regulation by androgen treatment. J Clin Endocrin Metab. 2004; 89: 5245-5255.
[31]
Sinha-Hikim I, Cornford M, Gaytan H, Lee ML, Bhasin S. Effects of Testosterone Supplementation on Skeletal Muscle Fiber Hypertrophy and Satellite Cells in Community-Dwelling Older Men. J Clin Endocrinol Metab. 2006; 91 (8): 3024-3033.
[32]
Filho JCJCS, Vanderlei LCM, Camargo RCT, Francischeti FA, Belangero WD, Pai VD. Effects of the anabolic steroid nandrolone on the soleum muscle of rats submitted to physical training through swimming: histological, histochemical and morphometrical study. Rev Bras Med Esporte. 2006; 12, (5): 243-247.
[33]
Tanno AP, das Neves VJ, Rosa KT, et al. Nandrolone and resistance training induce heart remodeling: role of fetal genes and implications for cardiac pathophysiolog­y. Life Sci. 2011; 89: 631–637.
[34]
Kadi F. Cellular and molecular mechanisms responsible for the action of testosterone on human skeletal muscle. A basis for illegal performance enhancement. Br J Pharmacol. 2008; 154 (3): 522–528.
[35]
Cullen MJ, Johnson MA, Mastaglia FL. Pathological reactions of skeletal muscle, Ch: 3, in, Mastaglia, F. L. and Walton, l. (eds.) Skeltal Muscle Pathology, Churchill Livingstone, Edinburgh, London, New York, Philadelphia, Sanfrancisco, Sydney, Toronto. 2001; P: 123-184.
[36]
Kuang S, Rudnicki MA. The emerging biology of satellite cells and their therapeutic potential. Trends Mol. Med. 2008; 14: 82-91.
[37]
Ribeiro BG, Fernandes K PS, Silva MT, Sierra SO, Bussadori SK, Mesquita-Ferrari R A. Effects of nandrolone decanoate on the viability of muscle satellite cells during the differentiation process. Fisioterapia e Pesquisa. 2014; 21 (1): 16-20.
[38]
Vicencio JM, Estrada M, Galvis D, et al. Anabolic androgenic steroids and intracellular calcium signaling: a mini review on mechanisms and physiological implications. Mini Rev Med Chem. 2011; 11 (5): 390-398.
[39]
Sequeira V, Nijenkamp LL, Regan JA, van der Velden J. The physiological role of cardiac cytoskeleton and its alterations in heart failure. Biochim Biophys Acta. 2014; 1838: 700-722.
[40]
Montera MW, Drumon C, Takiya C, Mesquita CT, Dohmann HFR, Mady C. Correlation of myocardial interstitial collagen in the right ventricular septum with ventricular function of patients with ischemic cardiomyopathy. Arq. Bras. Cardiol. 2009; 92: 52-60.
[41]
Mann CJ, Perdiguero E, Kharraz Y, et al. Aberrant repair and fibrosis development in skeletal muscle. Skelet Muscle. 2011; 4 (1): 21.
[42]
Sadowska-Krepa E, Kłapcińska B, Jagsz S, Sobczak., Chrapusta SJ, Chalimoniuk M, Grieb P, Proprzęcki. S, Langfort J. High-Dose Testosterone Propionate Treatment Reverses the Effects of Endurance Training on Myocardial Antioxidant Defenses in Adolescent Male Rats. Cardiovasc Toxicol. 2011; 11: 118-127.
[43]
Satoh K, Gotoh T, Yamashita K. Morphological effects of an anabolic steroid on muscle fibres of the diaphragm in mice. J Electron Microsc. 2000; 49 (4): 531-538.
[44]
Hassan NA, Salem MF, Sayed MA. Doping and effects of anabolic androgenic steroids on the heart: histological, ultrastructural, and echocardiographic assessment in strength athletes. Hum Exp Toxicol. 2009; 28 (5): 273-283.
[45]
Kavazis AN, Alvarez S, Talbert E, Lee Y, Powers SK. Exercise training induces a cardioprotective phenotype and alterations in cardiac subsarcolemmal and intermyofibrillar mitochondrial proteins. Am J Physiol Heart Circ Physiol. 2009; 297: H144–H152.
[46]
Baines CP. The cardiac mitochondrion: nexus of stress. Annu Rev Physiol. 2010; 72: 61-80.
[47]
Kroemer G, Galluzzi L, Vandenabeele P, et al. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death. Cell Death and Differentiation. 2009; 16: 3–11.
[48]
Chiong M, Wang ZV, Pedrozo Z, et al. Cardiomyocyte death: mechanisms and translational implications. Cell Death Dis. 2011; 2: e244.
[49]
Mayada RF, Taghred MS, Haytham AA. Boldenone-induced apoptotic, structural, and functional alterations in the liver of rabbits. World Rabbit Sci. 2015, 23: 39-46.
[50]
Lizotte E, Grandy SA, Tremblay A, Allen BG, Fiset C. Expression, distribution and regulation of sex steroid hormone receptors in mouse heart. Cell Physiol Biochem. 2009; 23: 75–86.
[51]
Chaves EA, Fortunato RS, Carvalho DP, Nascimento JH, Oliveira MF. Exercise-induced cardioprotection is impaired by anabolic steroid treatment through a redox-dependent mechanism. J Steroid Biochem Mol Biol. 2013; 138: 267-272.
Browse journals by subject