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Prolonged treatment with the anabolic–androgenic steroid stanozolol increases antioxidant defences in rat skeletal muscle

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Abstract

Testosterone and its synthetic derivatives anabolic–androgenic steroids have been shown to increase skeletal muscle work capacity and fatigue resistance, but the molecular basis for these effects remains uncertain. Since muscle performance has been related to redox status of exercising muscles, this investigation was aimed at testing whether a treatment with suprapharmacological doses of the anabolic–androgenic steroid stanozolol, (2 mg/kg body weight, 5 days/week, for 8 weeks), either alone or in conjunction with treadmill training (12 weeks), enhanced antioxidant defences in rat muscles. Stanozolol treatment did not modify thiobarbituric acid reactive substances and glutathione content in soleus and extensor digitorum longus (EDL) homogenates. In soleus from sedentary rats, superoxide dismutase and glutathione reductase activities were increased by 25% (P < 0.05) and by 40% (P < 0.01) after stanozolol administration, whereas catalase and glutathione peroxidase activities were not modified. This response was similar to that induced by training alone. In EDL from sedentary rats, stanozolol increased only superoxide dismutase activity (20%, P < 0.05). In no case, the effects of steroid administration and training were additive. HSP72 levels were up-regulated in soleus (1.5-fold, P < 0.01) and EDL (threefold, P < 0.001) following training but remained unchanged after stanozolol treatment. Endurance capacity, assessed in a treadmill endurance test, was similar for treated and control rats. We conclude that stanozolol treatment increases antioxidant capacity in selected skeletal muscles from sedentary rats. However, the steroid was not effective in improving endurance capacity or enhancing the training effects on muscle antioxidant defence systems.

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References

  1. Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    Article  CAS  PubMed  Google Scholar 

  2. Ahlbom E, Prins GS, Ceccatelli S (2001) Testosterone protects cerebellar granule cells from oxidative stress-induced cell death through a receptor mediated mechanism. Brain Res 892:255–262

    Article  CAS  PubMed  Google Scholar 

  3. Axell AM, MacLean HE, Plant DR, Harcourt LJ, Davis JA, Jimenez M, Handelsman DJ, Lynch GS, Zajac JD (2006) Continuous testosterone administration prevents skeletal muscle atrophy and enhances resistance to fatigue in orchidectomized male mice. Am J Physiol Endocrinol Metab 291:E506–E516

    Article  CAS  PubMed  Google Scholar 

  4. Bhasin S, Calof OM, Storer TW, Lee ML, Mazer NA, Jasuja R, Montori VM, Gao W, Dalton JT (2006) Drug insight: testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging. Nat Clin Pract Endocrinol Metab 2:146–159

    Article  CAS  PubMed  Google Scholar 

  5. Boada LD, Zumbado M, Torres S, Lopez A, Diaz-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

    Article  CAS  PubMed  Google Scholar 

  6. Bombardier E, Vigna C, Iqbal S, Tiidus PM, Tupling AR (2009) Effects of ovarian sex hormones and downhill running on fiber-type-specific HSP70 expression in rat soleus. J Appl Physiol 106:2009–2015

    Article  CAS  PubMed  Google Scholar 

  7. Carlberg I, Mannervik B (1985) Glutathione reductase. Methods Enzymol 113:484–490

    Article  CAS  PubMed  Google Scholar 

  8. De Gooyer ME, Oppers-Tiemissen HM, Leysen D, Verheul HA, Kloosterboer HJ (2003) Tibolone is not converted by human aromatase to 7alpha-methyl-17alpha-ethynylestradiol (7alpha-MEE): analyses with sensitive bioassays for estrogens and androgens and with LC-MSMS. Steroids 68:235–243

    Article  PubMed  Google Scholar 

  9. Delgado J, Saborido A, Moran M, Megias A (1999) Chronic and acute exercise do not alter Ca2+ regulatory systems and ectonucleotidase activities in rat heart. J Appl Physiol 87:152–160

    CAS  PubMed  Google Scholar 

  10. Delp MD, Duan C (1996) Composition and size of type I, IIA, IID/X, and IIB fibers and citrate synthase activity of rat muscle. J Appl Physiol 80:261–270

    CAS  PubMed  Google Scholar 

  11. Egginton S (1987) Effects of an anabolic hormone on striated muscle growth and performance. Pflugers Arch 410:349–355

    Article  CAS  PubMed  Google Scholar 

  12. Feldkoren BI, Andersson S (2005) Anabolic-androgenic steroid interaction with rat androgen receptor in vivo and in vitro: a comparative study. J Steroid Biochem Mol Biol 94:481–487

    Article  CAS  PubMed  Google Scholar 

  13. Flohe L, Gunzler WA (1984) Assays of glutathione peroxidase. Methods Enzymol 105:114–121

    Article  CAS  PubMed  Google Scholar 

  14. Gomez-Cabrera MC, Domenech E, Vina J (2008) Moderate exercise is an antioxidant: upregulation of antioxidant genes by training. Free Radic Biol Med 44:126–131

    Article  CAS  PubMed  Google Scholar 

  15. Gonzalez B, Hernando R, Manso R (2000) Anabolic steroid and gender-dependent modulation of cytosolic HSP70s in fast- and slow-twitch skeletal muscle. J Steroid Biochem Mol Biol 74:63–71

    Article  CAS  PubMed  Google Scholar 

  16. Griffith OW (1980) Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Anal Biochem 106:207–212

    Article  CAS  PubMed  Google Scholar 

  17. Hartgens F, Kuipers H (2004) Effects of androgenic-anabolic steroids in athletes. Sports Med 34:513–554

    Article  PubMed  Google Scholar 

  18. Hernando R, Manso R (1997) Muscle fibre stress in response to exercise: synthesis, accumulation and isoform transitions of 70-kDa heat-shock proteins. Eur J Biochem 243:460–467

    Article  CAS  PubMed  Google Scholar 

  19. Hourde C, Jagerschmidt C, Clement-Lacroix P, Vignaud A, Ammann P, Butler-Browne GS, Ferry A (2009) Androgen replacement therapy improves function in male rat muscles independently of hypertrophy and activation of the Akt/mTOR pathway. Acta Physiol (Oxf) 195:471–482

    Article  CAS  Google Scholar 

  20. Ji LL (2008) Modulation of skeletal muscle antioxidant defense by exercise: role of redox signaling. Free Radic Biol Med 44:142–152

    Article  CAS  PubMed  Google Scholar 

  21. Kadi F (2008) Cellular and molecular mechanisms responsible for the action of testosterone on human skeletal muscle. A basis for illegal performance enhancement. Br J Pharmacol 154:522–528

    Article  CAS  PubMed  Google Scholar 

  22. Kicman AT (2008) Pharmacology of anabolic steroids. Br J Pharmacol 154:502–521

    Article  CAS  PubMed  Google Scholar 

  23. Laughlin MH, Armstrong RB (1983) Rat muscle blood flows as a function of time during prolonged slow treadmill exercise. Am J Physiol 244:H814–H824

    CAS  PubMed  Google Scholar 

  24. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) c. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  25. Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474

    Article  CAS  PubMed  Google Scholar 

  26. Molano F, Saborido A, Delgado J, Moran M, Megias A (1999) Rat liver lysosomal and mitochondrial activities are modified by anabolic-androgenic steroids. Med Sci Sports Exerc 31:243–250

    Article  CAS  PubMed  Google Scholar 

  27. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  CAS  PubMed  Google Scholar 

  28. Orlando R, Caruso A, Molinaro G, Motolese M, Matrisciano F, Togna G, Melchiorri D, Nicoletti F, Bruno V (2007) Nanomolar concentrations of anabolic-androgenic steroids amplify excitotoxic neuronal death in mixed mouse cortical cultures. Brain Res 1165:21–29

    Article  CAS  PubMed  Google Scholar 

  29. Papaconstantinou AD, Umbreit TH, Goering PL, Brown KM (2002) Effects of 17 alpha-methyltestosterone on uterine morphology and heat shock protein expression are mediated through estrogen and androgen receptors. J Steroid Biochem Mol Biol 82:305–314

    Article  CAS  PubMed  Google Scholar 

  30. Pey A, Saborido A, Blazquez I, Delgado J, Megias 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

    Article  CAS  PubMed  Google Scholar 

  31. Pinthus JH, Bryskin I, Trachtenberg J, Lu JP, Singh G, Fridman E, Wilson BC (2007) Androgen induces adaptation to oxidative stress in prostate cancer: implications for treatment with radiation therapy. Neoplasia 9:68–80

    Article  CAS  PubMed  Google Scholar 

  32. Powers SK, Jackson MJ (2008) Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production. Physiol Rev 88:1243–1276

    Article  CAS  PubMed  Google Scholar 

  33. Reid MB (2001) Nitric oxide, reactive oxygen species, and skeletal muscle contraction. Med Sci Sports Exerc 33:371–376

    Article  CAS  PubMed  Google Scholar 

  34. Reid MB (2008) Free radicals and muscle fatigue: Of ROS, canaries, and the IOC. Free Radic Biol Med 44:169–179

    Article  CAS  PubMed  Google Scholar 

  35. Shahidi NT (2001) A review of the chemistry, biological action, and clinical applications of anabolic-androgenic steroids. Clin Ther 23:1355–1390

    Article  CAS  PubMed  Google Scholar 

  36. Smolka MB, Zoppi CC, Alves AA, Silveira LR, Marangoni S, Pereira-Da-Silva L, Novello JC, Macedo DV (2000) HSP72 as a complementary protection against oxidative stress induced by exercise in the soleus muscle of rats. Am J Physiol Regul Integr Comp Physiol 279:R1539–R1545

    CAS  PubMed  Google Scholar 

  37. Tam NN, Gao Y, Leung YK, Ho SM (2003) Androgenic regulation of oxidative stress in the rat prostate: involvement of NAD(P)H oxidases and antioxidant defense machinery during prostatic involution and regrowth. Am J Pathol 163:2513–2522

    CAS  PubMed  Google Scholar 

  38. Tamaki T, Uchiyama S, Uchiyama Y, Akatsuka A, Roy RR, Edgerton VR (2001) Anabolic steroids increase exercise tolerance. Am J Physiol Endocrinol Metab 280:E973–E981

    CAS  PubMed  Google Scholar 

  39. Zhou LZ, Johnson AP, Rando TA (2001) NF kappa B and AP-1 mediate transcriptional responses to oxidative stress in skeletal muscle cells. Free Radic Biol Med 31:1405–1416

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors are grateful to Zambon S.A. (Barcelona) for kindly providing us with stanozolol and to L. Soblechero for her technical assistance in HSP72 quantification. This work was supported by research grants from the Spanish Ministry of Education and Science (BFU 2005-08506-C02-02) and from the Santander-Complutense Foundation (PR27/05-13996).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology I, Faculty of Biology, Complutense University, 28040, Madrid, Spain

    J. Delgado & A. Megías

  2. Department of Biochemistry and Molecular Biology I, Faculty of Chemistry, Complutense University, 28040, Madrid, Spain

    A. Saborido

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  1. J. Delgado
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Correspondence to A. Megías.

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Delgado, J., Saborido, A. & Megías, A. Prolonged treatment with the anabolic–androgenic steroid stanozolol increases antioxidant defences in rat skeletal muscle. J Physiol Biochem 66, 63–71 (2010). https://doi.org/10.1007/s13105-010-0010-1

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  • DOI: https://doi.org/10.1007/s13105-010-0010-1

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