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DOI: 10.1055/s-0035-1548941
High-intensity Exercise Modifies the Effects of Stanozolol on Brain Oxidative Stress in Rats
Publication History
accepted after revision 14 March 2015
Publication Date:
07 August 2015 (online)
Abstract
We analyzed the effects of high-intensity exercise (HIE) and anabolic androgenic steroids (AAS) on brain redox status. 40 male Wistar rats were randomly distributed in 4 experimental groups (n=10) with or without HIE and with or without weekly Stanozolol administration. Thiobarbituric acid-reactive substances (TBARs) and protein carbonyl content (PCC) were assessed. Total superoxide dismutase (tSOD), manganese superoxide dismutase (Mn-SOD), copper/zinc superoxide dismutase (CuZn-SOD) and catalase (CAT) activities were measured. Finally, protein expression levels of glutathione peroxidase (GPx), NAD(P)H dehydrogenase, Quinone 1 (NQO1), NF-E2-Related Factor 2 (Nrf2), glial fibrillary acidic protein (GFAP), nuclear factor kappa β p65 (NF-κβ) and signal transducer and activator of transcription 3 were determined. Brain PCC concentrations were lower in the HIE groups compared to the untrained controls, whereas CAT activity was higher (both, p<0.01). Both HIE and AAS groups exhibited higher expression levels of GFAP and GPx, but lower NQO1 levels (all, p<0.05). There were increased expression levels of NF-κβ in the AAS groups (p<0.01). In addition, there was increased expression of Nrf2 in the HIE groups (p<0.001). HIE*AAS interactions were found on TBARs content and GFAP expression, with HIE downregulating and upregulating AAS-mediated increases in TBARs and GFAP, respectively (p<0.05). Overall, HIE appeared to reduce the AAS-mediated negative effect on brain redox status.
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References
- 1 Acikgoz O, Aksu I, Topcu A, Kayatekin BM. Acute exhaustive exercise does not alter lipid peroxidation levels and antioxidant enzyme activities in rat hippocampus, prefrontal cortex and striatum. Neurosci Lett 2006; 406: 148-151
- 2 Aebi H. Catalase in vitro. Methods Enzymol 1984; 105: 121-126
- 3 Aguiar AS, Boemer G, Rial D, Cordova FM, Mancini G, Walz R, de Bem AF, Latini A, Leal RB, Pinho RA, Prediger RDS. High-intensity physical exercise disrupts implicit memory in mice: Involvement of the striatal glutathione antioxidant system and intracellular signaling. Neuroscience 2010; 171: 1216-1227
- 4 Aparicio VA, Nebot E, Kapravelou G, Sanchez C, Porres JM, Lopez Jurado M, Aranda P. Resistance training reduces the metabolic acidosis and hepatic and renal hypertrophy caused by the consumption of a high protein diet in rats. Nutr Hosp 2011; 26: 1478-1486
- 5 Aparicio VA, Nebot E, Porres JM, Ortega FB, Heredia JM, Lopez-Jurado M, Ramirez PA. Effects of high-whey-protein intake and resistance training on renal, bone and metabolic parameters in rats. Br J Nutr 2011; 105: 836-845
- 6 Aparicio VA, Sanchez C, Ortega FB, Nebot E, Kapravelou G, Porres JM, Aranda P. Effects of the dietary amount and source of protein, resistance training and anabolic-androgenic steroids on body weight and lipid profile of rats. Nutr Hosp 2013; 28: 127-136
- 7 Aparicio VA, Tassi M, Nebot E, Camiletti-Moiron D, Ortega E, Porres JM, Aranda P. High-intensity exercise may compromise renal morphology in rats. Int J Sports Med 2014; DOI: 10.1055/s-0033-1354383.
- 8 Aydin C, Sonat F, Sahin SK, Cangul IT, Ozkaya G. Long term dietary restriction ameliorates swimming exercise-induced oxidative stress in brain and lung of middle-aged rat. Indian J Exp Biol 2009; 47: 24-31
- 9 Baillet A, Chanteperdrix V, Trocme C, Casez P, Garrel C, Besson G. The role of oxidative stress in amyotrophic lateral sclerosis and Parkinson’s disease. Neurochem Res 2010; 35: 1530-1537
- 10 Ballard TP, Melby CL, Camus H, Cianciulli M, Pitts J, Schmidt S, Hickey MS. Effect of resistance exercise, with or without carbohydrate supplementation, on plasma ghrelin concentrations and postexercise hunger and food intake. Metabolism 2009; 58: 1191-1199
- 11 Basaria S, Wahlstrom JT, Dobs AS. Clinical review 138: Anabolic-androgenic steroid therapy in the treatment of chronic diseases. J Clin Endocrinol Metab 2001; 86: 5108-5117
- 12 Camiletti-Moiron D, Aparicio VA, Aranda P, Radak Z. Does exercise reduce brain oxidative stress? A systematic review. Scand J Med Sci Sports 2013; 23: e202-e212
- 13 Celec P, Jani P, Smrekova L, Mrlian A, Kudela M, Hodosy J, Boor P, Kristova V, Jakubovsky J, Jezova D, Halcak L, Bozek P, Slamova J, Ulicna O, Hojsik D, Jurkovicova I. Effects of anabolic steroids and antioxidant vitamins on ethanol-induced tissue injury. Life Sci 2003; 74: 419-434
- 14 Chan PH. Role of oxidants in ischemic brain damage. Stroke 1996; 27: 1124-1129
- 15 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
- 16 Chaves EA, Pereira-Junior PP, Fortunato RS, Masuda MO, de Carvalho AC, de Carvalho DP, Oliveira MF, Nascimento JH. Nandrolone decanoate impairs exercise-induced cardioprotection: role of antioxidant enzymes. J Steroid Biochem Mol Biol 2006; 99: 223-230
- 17 Cunha TS, Tanno AP, Costa Sampaio Moura MJ, Marcondes FK. Influence of high-intensity exercise training and anabolic androgenic steroid treatment on rat tissue glycogen content. Life Sci 2005; 77: 1030-1043
- 18 Dalla Corte CL, de Carvalho NR, Amaral GP, Puntel GO, Silva LF, Retamoso LT, Royes LF, Bresciani GB, da Cruz IB, Rocha JB, Barrio Lera JP, Soares FA. Antioxidant effect of organic purple grape juice on exhaustive exercise. Appl Physiol Nutr Metab 2013; 38: 558-565
- 19 Darnell Jr JE. STATs and gene regulation. Science 1997; 277: 1630-1635
- 20 Davies KJ. Intracellular proteolytic systems may function as secondary antioxidant defenses: an hypothesis. J Free Radic Biol Med 1986; 2: 155-173
- 21 de Senna PN, Ilha J, Baptista PP, do Nascimento PS, Leite MC, Paim MF, Goncalves CA, Achaval M, Xavier LL. Effects of physical exercise on spatial memory and astroglial alterations in the hippocampus of diabetic rats. Metab Brain Dis 2011; 26: 269-279
- 22 Deschenes MR, Kraemer WJ. Performance and physiologic adaptations to resistance training. Am J Phys Med Rehabil 2002; 81: S3-S16
- 23 Dimauro J, Balnave RJ, Shorey CD. Effects of anabolic steroids and high intensity exercise on rat skeletal muscle fibres and capillarization. A morphometric study. Eur J Appl Physiol 1992; 64: 204-212
- 24 Eng LF, Ghirnikar RS, Lee YL. Glial fibrillary acidic protein: GFAP-thirty-one years (1969–2000). Neurochem Res 2000; 25: 1439-1451
- 25 Estoppey-Stojanovski L. Position of the Council of Europe on the protection of animals. Dev Biol Stand 1986; 64: 3-5
- 26 Fontana K, Campos GE, Staron RS, da Cruz-Hofling MA. Effects of anabolic steroids and high-intensity aerobic exercise on skeletal muscle of transgenic mice. PLoS One 2013; 8: e80909
- 27 George L, Lokhandwala MF, Asghar M. Exercise activates redox-sensitive transcription factors and restores renal D1 receptor function in old rats. Am J Physiol Renal Physiol 2009; 297: F1174-F1180
- 28 Halliwell B. Oxidative stress and neurodegeneration: where are we now?. J Neurochem 2006; 97: 1634-1658
- 29 Harmer PA. Anabolic-androgenic steroid use among young male and female athletes: is the game to blame?. Br J Sports Med 2010; 44: 26-31
- 30 Harriss DJ, Atkinson G. Ethical standards in sport and exercise science research: 2014 update. Int J Sports Med 2013; 34: 1025-1028
- 31 Hartgens F, Kuipers H. Effects of androgenic-anabolic steroids in athletes. Sports Med 2004; 34: 513-554
- 32 Houston MC, Fazio S, Chilton FH, Wise DE, Jones KB, Barringer TA, Bramlet DA. Nonpharmacologic treatment of dyslipidemia. Prog Cardiovasc Dis 2009; 52: 61-94
- 33 Jung JE, Kim GS, Narasimhan P, Song YS, Chan PH. Regulation of Mn-superoxide dismutase activity and neuroprotection by STAT3 in mice after cerebral ischemia. J Neurosci 2009; 29: 7003-7014
- 34 Lambertucci RH, Levada-Pires AC, Rossoni LV, Curi R, Pithon-Curi TC. Effects of aerobic exercise training on antioxidant enzyme activities and mRNA levels in soleus muscle from young and aged rats. Mech Ageing Dev 2007; 128: 267-275
- 35 Levine RL, Williams JA, Stadtman ER, Shacter E. Carbonyl assays for determination of oxidatively modified proteins. Methods Enzymol 1994; 233: 346-357
- 36 Levy DE, Lee CK. What does Stat3 do?. J Clin Invest 2002; 109: 1143-1148
- 37 Li J, Wang Y. Effect of different methods of hypoxic exercise training on free radical oxidation and antioxidant enzyme activity in the rat brain. Biomed Rep 2013; 1: 925-929
- 38 Liu GH, Qu J, Shen X. NF-kappaB/p65 antagonizes Nrf2-ARE pathway by depriving CBP from Nrf2 and facilitating recruitment of HDAC3 to MafK. Biochim Biophys Acta 2008; 1783: 713-727
- 39 Liu J, Yeo HC, Overvik-Douki E, Hagen T, Doniger SJ, Chyu DW, Brooks GA, Ames BN. Chronically and acutely exercised rats: biomarkers of oxidative stress and endogenous antioxidants. J Appl Physiol 2000; 89: 21-28
- 40 Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193: 265-275
- 41 Marosi K, Bori Z, Hart N, Sarga L, Koltai E, Radak Z, Nyakas C. Long-term exercise treatment reduces oxidative stress in the hippocampus of aging rats. Neuroscience 2012; 226: 21-28
- 42 Mattson MP, Magnus T. Ageing and neuronal vulnerability. Nat Rev Neurosci 2006; 7: 278-294
- 43 Muthusamy VR, Kannan S, Sadhaasivam K, Gounder SS, Davidson CJ, Boeheme C, Hoidal JR, Wang L, Rajasekaran NS. Acute exercise stress activates Nrf2/ARE signaling and promotes antioxidant mechanisms in the myocardium. Free Radic Biol Med 2012; 52: 366-376
- 44 Novaes Gomes FG, Fernandes J, Vannucci Campos D, Cassilhas RC, Viana GM, D’Almeida V, de Moraes Rego MK, Buainain PI, Cavalheiro EA, Arida RM. The beneficial effects of strength exercise on hippocampal cell proliferation and apoptotic signaling is impaired by anabolic androgenic steroids. Psychoneuroendocrinology 2014; 50: 106-117
- 45 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: 202-214
- 46 Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95: 351-358
- 47 Pey A, Saborido A, Blazquez I, Delgado J, Megias A. 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 2003; 87: 269-277
- 48 Pope Jr HG, Katz DL. Affective and psychotic symptoms associated with anabolic steroid use. Am J Psychiat 1988; 145: 487-490
- 49 Qiao D, Hou L, Liu X. Influence of intermittent anaerobic exercise on mouse physical endurance and antioxidant components. Br J Sports Med 2006; 40: 214-218
- 50 Ramos-Gomez M, Kwak MK, Dolan PM, Itoh K, Yamamoto M, Talalay P, Kensler TW. Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in nrf2 transcription factor-deficient mice. Proc Natl Acad Sci USA 2001; 98: 3410-3415
- 51 Riezzo I, De Carlo D, Neri M, Nieddu A, Turillazzi E, Fineschi V. Heart disease induced by AAS abuse, using experimental mice/rats models and the role of exercise-induced cardiotoxicity. Mini Rev Med Chem 2011; 11: 409-424
- 52 Rodrigues L, Dutra MF, Ilha J, Biasibetti R, Quincozes-Santos A, Leite MC, Marcuzzo S, Achaval M, Goncalves CA. Treadmill training restores spatial cognitive deficits and neurochemical alterations in the hippocampus of rats submitted to an intracerebroventricular administration of streptozotocin. J Neural Transm 2010; 117: 1295-1305
- 53 Rosa EF, Takahashi S, Aboulafia J, Nouailhetas VL, Oliveira MG. Oxidative stress induced by intense and exhaustive exercise impairs murine cognitive function. J Neurophysiol 2007; 98: 1820-1826
- 54 Saborido A, Naudi A, Portero-Otin M, Pamplona R, Megias A. Stanozolol treatment decreases the mitochondrial ROS generation and oxidative stress induced by acute exercise in rat skeletal muscle. J Appl Physiol 2011; 110: 661-669
- 55 Safdar A, deBeer J, Tarnopolsky MA. Dysfunctional Nrf2-Keap1 redox signaling in skeletal muscle of the sedentary old. Free Radic Biol Med 2010; 49: 1487-1493
- 56 Salmina AB. Neuron-glia interactions as therapeutic targets in neurodegeneration. J Alzheimers Dis 2009; 16: 485-502
- 57 Shahidi NT. A review of the chemistry, biological action, and clinical applications of anabolic-androgenic steroids. Clin Ther 2001; 23: 1355-1390
- 58 Stefani GP, Nunes RB, Dornelles AZ, Alves JP, Piva MO, Domenico MD, Rhoden CR, Lago PD. Effects of creatine supplementation associated with resistance training on oxidative stress in different tissues of rats. J Int Soc Sports Nutr 2014; 11: 11
- 59 Sun M, Shen W, Zhong M, Wu P, Chen H, Lu A. Nandrolone attenuates aortic adaptation to exercise in rats. Cardiovasc Res 2013; 97: 686-695
- 60 Tsakiris T, Angelogianni P, Tesseromatis C, Tsakiris S, Tsopanakis C. Alterations in antioxidant status, protein concentration, acetylcholinesterase, Na+, K+-ATPase, and Mg2+-ATPase activities in rat brain after forced swimming. Int J Sports Med 2006; 27: 19-24
- 61 Tsou YH, Shih CT, Ching CH, Huang JY, Jen CJ, Yu L, Kuo YM, Wu FS, Chuang JI. Treadmill exercise activates Nrf2 antioxidant system to protect the nigrostriatal dopaminergic neurons from MPP(+) toxicity. Exp Neurol 2015; 263: 50-62
- 62 Tugyan K, Ozbal S, Cilaker S, Kiray M, Pekcetin C, Ergur BU, Kumral A. Neuroprotective effect of erythropoietin on nandrolone decanoate-induced brain injury in rats. Neurosci Lett 2013; 533: 28-33
- 63 Ukeda H, Maeda S, Ishii T, Sawamura M. Spectrophotometric assay for superoxide dismutase based on tetrazolium salt 3′–1–(phenylamino)-carbonyl–3, 4-tetrazolium]-bis(4-methoxy-6-nitro)benzenesulfonic acid hydrate reduction by xanthine-xanthine oxidase. Anal Biochem 1997; 251: 206-209
- 64 Varamenti EI, Kyparos A, Veskoukis AS, Bakou M, Kalaboka S, Jamurtas AZ, Koutedakis Y, Kouretas D. Oxidative stress, inflammation and angiogenesis markers in elite female water polo athletes throughout a season. Food Chem Toxicol 2013; 61: 3-8
- 65 Whybrow S, Hughes DA, Ritz P, Johnstone AM, Horgan GW, King N, Blundell JE, Stubbs RJ. The effect of an incremental increase in exercise on appetite, eating behaviour and energy balance in lean men and women feeding ad libitum. Br J Nutr 2008; 100: 1109-1115
- 66 Williams MA, Haskell WL, Ades PA, Amsterdam EA, Bittner V, Franklin BA, Gulanick M, Laing ST, Stewart KJ. American Heart Association Council on Clinical C, American Heart Association Council on Nutrition PA, Metabolism. Resistance exercise in individuals with and without cardiovascular disease: 2007 update: a scientific statement from the American Heart Association Council on Clinical Cardiology and Council on Nutrition, Physical Activity, and Metabolism. Circulation 2007; 116: 572-584
- 67 Radak Z, Asano K, Kizaki T, Oh-ishi S, Inoue M, Ohno H. Acute bout of exercise does not alter the antioxidant enzyme status and lipid peroxidation in rat hippocampus and cerebellum. Pathophysiology 1995; 2: 243-245
- 68 Zhang M, An C, Gao Y, Leak RK, Chen J, Zhang F. Emerging roles of Nrf2 and phase II antioxidant enzymes in neuroprotection. Prog Neurobiol 2013; 100: 30-47