Abstract
The objective of this study was to evaluate the effects of different protocols (P1, P2, and P3) of boldenone undecylenate (BU) and stanozolol (ST) on markers of liver and kidney function and variables of oxidative stress in these organs. For this, 54 male Wistar rats were divided into nine groups of six animals each. Each animal received intramuscularly 5.0 mg kg−1 of BU or ST once a week for 4 weeks (P1); 2.5 mg kg−1 of BU or ST once a week for 8 weeks (P2); and 1.25 mg kg−1 of BU or ST once a week for 12 weeks (P3). For each protocol, a control group was used, and they received 0.1 ml of olive oil intramuscularly. Blood and fragments of liver and kidney were collected for alanine aminotransferase activity (ALT), alkaline phosphatase, albumin, creatinine, cholesterol, total protein, triglycerides, urea, reactive oxygen species, thiobarbituric acid reactive substances, total thiols, and glutathione evaluation. The results show that the BU in doses of 5 (day 30) and 2.5 mg kg−1 (day 60) changes the ALT seric activity, possibly showing a hepatotoxic effect. High doses of BU may lead to increased levels of cholesterol (protocol P1) possibly due to inhibition of the normal steroid biosynthesis process. All protocols used caused changes in the redox balance of the organs studied (except in the liver, protocol P2), which indicates that these drugs might be harmful even at low doses.
Similar content being viewed by others
References
Shahidi N (2001) A review of the chemistry, biological action, and clinical applications of anabolic–androgenic steroids. Clin Ther 23:1355–1390
Kicman AT (2008) Pharmacology of anabolic steroids. Br J Pharmacol 154:502–521. doi:10.1038/bjp.2008.165
Guan F, Cornelius EU, Soma R, Youwen Y, Liu Y, Lia X (2010) High-throughput UHPLC MS/MS method for the detection, quantification and identification of fifty-five anabolic and androgenic steroids in equine plasma. J Mass Spectrom 45:1270–1279. doi:10.1002/jms.1816
Yersalis CE, Bahrke MS (1995) Anabolic–androgenic steroids. Sports Med 19:326–340
Yoshida EM, Karim MA, Shaikh JF, Soos JG, Erb SR (1994) At what price, glory? Severe cholestasis and acute renal failure in an athlete abusing stanozolol. CMAJ 151:791–793
Cerretani D, Neri M, Cantatore S, Costantino C, Irene R, Emanuela T, Vittorio F (2013) Looking for organ damages due to anabolic–androgenic steroids (AAS): Is oxidative stress the culprit? Mini Rev Org Chem 10:393–399
Riezzo I, Turillazzi E, Bello S, Cantatore S, Cerretani D, Di Paolo M, Fiaschi AI, Frati P, Neri M, Pedretti M, Fineschi V (2014) Chronic nandrolone administration promotes oxidative stress, induction of pro-inflammatory cytokine and TNF-α mediated apoptosis in the kidneys of CD1 treated mice. Toxicol Appl Pharmacol 280:97–106. doi:10.1016/j.taap.2014.06.031
World Anti-Doping Agency (WADA) The world anti doping code. The 2015 prohibited list international standard. https://wada-main-prod.s3.amazonaws.com/resources/files/wada-2015-prohibited-list-en.pdf
Soma LR, Uboh CE, Guan F, MC-Donnell S, Pack J (2007) Pharmacokinetics of boldenone and stanozolol and the results of quantification of anabolic and androgenic steroids in racehorses and nonrace horses. J Vet Pharmacol Therapeut 30:101–108. doi:10.1111/j.1365-2885.2007.00824.x
Verheyden K, Noppe H, Mortier V, Vercruysse J, Claerebout E, Van Immerseel F, Janssen CR, de Brabander HF (2007) Formation of boldenone and boldenone-analogues by maggots of Luciliasericata. Anal Chim Acta 586:163–170. doi:10.1016/j.aca.2006.11.009
Gryglik D, Olak M, Miller JS (2010) Photoderadation kinetics of androgenic steroids boldenone and trenbolone in aqueous solutions. J Photochem Photobiol 212:14–19. doi:10.1016/j.jphotochem.2010.03.005
Deshmukh N, Hussain I, Barker J, Petroczi A, Naughton D (2010) Analysis of anabolicsteroids in human hair using LC-MS/MS. Steroids 75:710–714. doi:10.1016/j.steroids.2010.04.007
Maini AA, Maxwell-Scott H, Marks DJ (2014) Severe alkalosis and hypokalemia with stanozolol misuse. Am J Emerg Med 32:196.e3–196.e4. doi:10.1016/j.ajem.2013.09.027
Frankenfeld SP, Oliveira LP, Ortenzi VH, Rego-Monteiro IC, Chaves EA, Ferreira AC, Leitão AC, Carvalho DP, Fortunato RS (2014) The anabolic androgenic steroid nandrolonedecanoate disrupts redox homeostasis in liver, heart and kidney of male Wistar rats. PLoS ONE 9:e102699. doi:10.1371/journal.pone.0102699
Neri M, Bello S, Bonsignore A, Cantatore S, Riezzo I, Turillazzi E, Fineschi V (2011) Anabolic androgenic steroids abuse and liver toxicity. MRMC 11:430–437
Ding N, Cruz P, Lim L, Thompson A, Desmond P (2013) Androgenic–anabolic steroid drug-induced liver injury. Intern Med J 43:215–216. doi:10.1111/imj.12054
Bejma J, Ramires P, Ji LL (2000) Free radical generation and oxidative stress with ageing and exercise: differential effects in the myocardium and liver. Acta Physiol Scand 169:343–351. doi:10.1046/j.1365-201x.2000.00745.x
Giorgio M, Trinei M, Migliaccio E, Pelicci PG (2007) Hydrogen peroxide: A metabolic by-product or a common mediator of ageing signals? Nat Ver Mol Cell Biol 8:722–728. doi:10.1038/nrm2240
Fernandez LL, Fornari LHT, Barbosa MV, Schroder N (2007) Ferro e neurodegeneração. Sci Med 17:218–224
Jones D (2008) Radical-free biology of oxidative stress. Am J Physiol Cell Physiol 295:C849–C868. doi:10.1152/ajpcell.00283.2008
Esterbauer H (1993) Cytotoxicity and genotoxicity of lipid-oxidation products. Am J Clin Nutr 57:779–785
Myhre O, Andersen JM, Aarnes H, Fonnum F (2003) Evaluation of the probes 2′,7′-dichlorofluorescin diacetate, luminol, and lucigenin as indicators of reactive species formation. Biochem Pharmacol 65:1575–1582
Bradford MMA (1976) A Rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein dye binding. Anal Biochem 72:248–254
Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358
Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77. doi:10.1016/0003-9861(59)90090-6
Boyne AF, Ellman GL (1972) A methodology for analysis of tissue sulfhydryl components. Anal Biochem 46:639–653
Welder AA, Robertson JW, Melchert RB (1995) Toxic effects of anabolic-androgenic steroids in primary rat hepatic cell cultures. J Pharmacol Toxicol Methods 33:187–195
Boada LD, Zumbado M, Torres S, López A, Díaz-Chico BN, Cabrera JJ, Luzardo OP (1999) Evaluation of acute and chronic hepatotoxic effects exerted by anabolic–androgenic steroid stanozolol in adult male rats. Arch Toxicol 73:465–472
Sileri P, Palmieri G, Gentileschi P, Perfetti A, Sica G, Venza M, Benavoli D, Gaspari AL (2005) Anabolic steroid nandrolone augments hepatic regenerative response in rats. Transplant Proc 37:4563–4566. doi:10.1016/j.transproceed.2005.10.123
Navarro CM, Montilla PM, Martín A, Jiménez J, Ultrilla PM (1993) Free radical scavenger and antihepatotoxic activity of Rosmarinus tomentosus. Planta Med 59:312–314
El-Moghazy M, Tousson E, Sakeran M (2012) Changes in the hepatic and renal structure and function after a growth promoter boldenone injection in rabbits. Anim Biol 62:171–180. doi:10.1002/jhet.5570420528
Rone MB, Fan J, Papadopoulos V (2009) Cholesterol transport in steroid biosynthesis: role of protein–protein interactions and implications in disease states. Biochim Biophys Acta 1791:646–658. doi:10.1016/j.bbalip.2009.03.001
Gårevik N, Skogastierna C, Rane A, Ekström L (2012) Single dose testosterone increases total cholesterol levels and induces the expression of HMG CoA reductase. Subst Abuse Treat Prev Policy 7:12. doi:10.1186/1747-597X-7-12
Gårevik N, Rane A, Björkhem-Bergman L, Ekström L (2014) Effects of different doses of testosterone on gonadotropins, 25-hydroxy vitamin D3, and blood lipids in healthy men. Subst Abuse Rehabil 5:121–127. doi:10.2147/SAR.S71285
Pey A, Saborido A, Blázquez I, Delgado J, Megías A (2003) Effects of prolonged stanozolol treatment on antioxidant enzyme activities, oxidative stress markers, and heat shock protein HSP72 levels in rat liver. J Steroid Biochem Mol Biol 87:269–277
Mayada R, Taghred M, Haytham A (2015) Boldenone-induced apoptotic, structural, and functional alterations in the liver of rabbits. World Rabbit Sci 23:39–46
Skogastierna C, Hotzen M, Rane A, Ekstrom L (2013) A supraphysiological dose of testosterone induces nitric oxide production and oxidative stress. Eur J Prev Cardiol 21:1049–1054. doi:10.1177/2047487313481755
Sadowska-Krepa E, Klapcinska B, Jagsz S, Chalimoniuk M, Chrapusta SJ, Wanke A, Grieb P, Langfort J (2013) Diverging oxidative damage and heat shock protein 72 responses to endurance training and chronic testosterone propionate treatment in three striated muscle types of adolescent male rats. J Physiol Pharmacol 64:639–647
Ogonovszky H, Sasvári M, Dosek A, Berkes I, Kaneko T, Tahara S, Nakamoto H, Goto S, Radák Z (2005) The effects of moderate, strenuous, and overtraining on oxidative stress markers and DNA repair in rat liver. Can J Appl Physiol 30:186–195
Carvalho M, Pontes H, Remião F, Bastos ML, Carvalho F (2010) Mechanisms underlying the hepatotoxic effects of ecstasy. Curr Pharm Biotechnol 11:476–495
Molano F, Saborido A, Delgado J, Morán M, Megías A (1999) Rat liver lysosomal and mitochondrial activities are modified by anabolic–androgenic steroids. Med Sci Sports Exerc 31:243–250
Chihuailaf RH, Contreras PA, Wittwer FG (2002) Patogénesisdelestrés oxidativo: consecuencias y evaluaciónensalud animal. Vet M 33:265–283
Martinez GR, Loureiro APM, Marques SA, Miyamoto S, Yamaguchi LF, Onuki J, Almeida EA, Garcia CCM, Barbosa LF, Medeiros MHG, Di Mascio P (2003) Oxidative and alkylating damage in DNA. Mutat Res 544:115–127. doi:10.1016/j.mrrev.2003.05.005
Uchida M, Shiraishi K, Naito Y, Torii Y, Nakamura Y, Osawa T (1999) Activation of stress signaling pathways by the end product of lipid peroxidation. 4-Hydroxy-2-nonenal is a potential inducer of intracellular peroxide production. J Biol Chem 274:2234–2242
Halliwell B, Cross CE (1994) Oxygen-derived species: their relation to human disease and environmental stress. Environ Health Perspect 102:5–12
Gul M, Kutay FZ, Temocin S, Hanninen O (2000) Cellular and clinical implications of glutathione. Indian J Exp Biol 38:625–634
Torres-Bugarín O, Covarrubias-Bugarín R, Zamora-Perez AL, Torres-Mendoza BM, García-Ulloa M, Martínez-Sandoval FG (2007) Anabolic androgenic steroids induce micronuclei in buccal mucosa cells of bodybuilders. Br J Sports Med 41:592–596. doi:10.1136/bjsm.2006.032474
Fischer WH, Keiwan A, Schmitt E, Stopper H (2001) Increased formations of micronuclei alter hormonal stimulation of cell proliferation in human breast cancer cells. Mutagenesis 16:209–212
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Dornelles, G.L., Bueno, A., de Oliveira, J.S. et al. Biochemical and oxidative stress markers in the liver and kidneys of rats submitted to different protocols of anabolic steroids. Mol Cell Biochem 425, 181–189 (2017). https://doi.org/10.1007/s11010-016-2872-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-016-2872-1