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Testosterone increases corpus cavernous smooth muscle cells in oxidative stress-induced rodents (Sprague-Dawley)



Abstract

Background: Nowadays, there are many researchers interested in the role of oxidative stress in the pathophysiological mechanism against erectile dysfunction. Oxidative stress occurs when there is an imbalance between pro-oxidant and the ability of the antioxidants to scavenge excess reactive oxygen species. The important role of oxidative stress in the pathophysiological mechanism of male and female infertility has been known.  However, its role in maintaining the integrity structure of penile erectile tissue especially corpus cavernous smooth muscle cell has not been investigated comprehensively yet. In another side, testosterone has a critical role in maintaining the integrity of the penile erectile tissue. Aim: This study aims to investigate the effect of oxidative stress condition on the administration of testosterone for increasing corpus cavernous smooth muscle cells. Methods: The experiment uses pretest-posttest control group design. Data were collected from 40 rodent’s strain SD (Sprague-Dawley). Ten penile organs were removed before stress, and 30 rodents given psychosocial stress for 6 weeks. After the third-week of stress, 10 penile organs were removed. At the beginning of the fourth week, 20 rodents were randomly divided into 2 groups: the control group (untreated mouse), were treated with an intramuscular aquabides injection and the case group were treated with intramuscular testosterone injection (case group). Five penile organs from each group were removed to observe the corpus cavernous smooth muscle cells number at the sixth weeks of the stress. During the six week stress, blood samples were collected for MDA and SOD measurement at the beginning, at the third week, and at the sixth week. Results: This study found that oxidative stress decreases the corpus cavernous smooth muscle cell (CCSM) number significantly. The number of CCSM before stress 20,20 ± 1,23, and after the third-week of stress is 14,20 ± 1,03 (P < 0,05). In addition, the administration of testosterone at the beginning of fourth-week of stress raises CCSM number significantly. The number of CCSM before treatment is 13,80 ± 0,84, and after treatment is 18,40 ± 1,14. Conclusion: There was a significant elevation of CCSM number without being affected by oxidative stress in this study.

 

Keywords: oxidative stress psychosocial stress MDA SOD testosterone corpus cavernous smooth muscle cell.

References

  1. Adachi, S., Kawamura, K., and Takemoto, K. 1993. Oxidative Damage of Nuclear DNA in Liver of Rats Exposed to Psychosocial Stress. Cancer Research. 53 (18): 4153-4155.
  2. Agarwal, A., Nandipati, K.C., Sharma, R.K., Zippe, C.D., Raina, R. 2006. Role of Oxidative Stress in the Pathophysiological Mechanism of Erectile Dysfunction. Journal of Andrology. 27 (3): 335: 347.
  3. Albina, J.E and Reichner, J.S. 1998. Role of Nitric Oxide in Mediation of Macrophage Cytotoxicity and Apoptosis. Cancer Metastasis Rev: 38-53.
  4. Aricioglu, A., Aykol, S., Yenikaya, E., Baykaner, K., Serdar-Alp, M., and Turkozkan, N. 1993. Investigation of Serum and Tissue Lipid Peroxidation and Serum Ascorbic Acid, and Iron Levels in Human Brain Tumour. Turkish Neurosurgery 3: 150-153.
  5. Bernatova, I and Csizmadiova, Z. 2006. Effect of Chronic Social Stress on Nitric Oxide Synthesis and Vascular Function in Rats with Family History of Hypertension. Life Sci. 78 (15): p. 1726-32.
  6. Bhasin, S., Taylor, W.E., Singh, R., Artaza, J., Sinha-Hikim, I., Jasuja, R., Choi, H., Gonzalez-Cadavid, N.F. 2003. The Mechanism of Androgen Effects On body composition: mesenchymal pluripotent cell as the target of androgen action. J Gerontol. 58: M1103-M1110.
  7. Bivalacqua, T.J., Usta, M.F., Champion, H.C., Kadowitz, P.J., Hellstrom, W.J. 2003. Endothelian dysfunction in erectile dysfunction: role of the endothelium in erectile physiology and disease. J Androl. 24: S17-S37.
  8. Braunstein, G.D. 2004. Testes. In; Greenspan, F.S. and Gardner, D.G. editors. Basic and Clinical Endocrinology. 7th. Ed. New York: McGraw-Hill. p. 478-508.
  9. Campbell, D.T., and Stanley, J.D. 1968. Experimental and Experiment Quasi Experimental Design for Research. Chicago.
  10. Chisu, V., Manca, P., Lepore, G., Gadau, S., Zedda, M., and Farina, V. 2006. Testosterone Induces Neuroprotection from Oxidative Stress. Effects on Catalase Activity and 3-Nitro-L-Tyrosine Incorporation into Alpha-Tubulin in a Mouse Neuroblastoma Cell line. Arch Ital Biol. 144 (2): 63-73.
  11. Conti, M., Moramd, P.C., Lecillain, P., Lemonnier, A. 1991. Improve Flurometric Determination of Malonaldehyde. J Clin Chem. 37 (7): 1273-1275.
  12. Dalle-Donne. I., Rossi, R., Colombo, R., Giustarini, D., and Milzani, A. 2006. Biomarkers of Oxidative Damage in Human Disease. Clinical Chemistry. 52 (4): 601-623.
  13. Dressler W. W., and Bindon J. R. (1997). Social Status, Social Context, and Arterial Blood Pressure. American Journal of Physical Anthropology, 102:55-66.
  14. Dröge, W. 2002. Free Radicals in the Physiological Control of Cell Function. Physiol Rev. 82: 47-95.
  15. Esquifino, A.I., Chacón, F., Jimenez, V., Reyes Toso, C.F., Cardinali, D. 2004. 24-Hour Changes in Circulating Prolactin, Follicle-Stimulating Hormone, Luteinizing Hormone and Testosterone in Male Rats Subjected to Social Isolation. Journal of Circadian Rhythms. 2: 1-6
  16. Evliyaoglu, Y., Kayrin, L., and Kaya, B. 1997. Effect of Pentoxifylline on Veno-occlusive Priapism-Induced Corporeal Tissule Lipid Peroxidation in Rat Mode. Urol Res. 25: 143-147.
  17. Facchinetti, F., and Ottolini, F. 2004. Stress and Preterm Delivery. Journal of Psychsomatic Obstetrics and Gynecology, 25:1-2.
  18. Flint, M.S., Baum, A., Chambers, W.H., and Jenkins, F.J. 2007. Induction of DNA Damage, Alteration of DNA Repair and Transcriptional Activation by Stress Hormones. Psychoneuroendocrinology. 32: 470-479.
  19. Garruto, R.M., Little, M., James, G., and Brown, D. 1999. Natural experimental models: the global search for biomedical paradigms among traditional, modernizing and modern populations. Proceedings of the National Academies of Science, 96:10536-10543.
  20. Gomori, G. 1950. Gomori’s One Step Trichrome Stain. Am J Clin Path. 20: 661-664.
  21. Goyal, H.O., Braden, T.D., Williams, C.S., Dalvi, P., Mansour, M.M., Williams, J.W., Bartol, F.F., Wiley, A.A., Birch, L., and Prins, G.S. 2004. Abnormal Morphology of the Penis in Male Rats Exposed Neonatally to Diethylstilbestrol Is Associated with Altered Profile of Estrogen Receptor-α Protein, but Not of Androgen Receptor Protein: A Developmental and Immunocytochemical Study. Biol of Repro. 70. 1504-1517.
  22. Guyton, A. C. and Hall, J. E. 2006. Textbook of Medical Physiology. 11th. Ed. Philadelphia: Elsevier Saunders. p. 996-1010.
  23. Halliwell, B., and Chirico, S. 1993. Lipid Peroxidation: Its Mechanism, Measurement, and Significance. Am J. Clin Nutr. 57: 715-725.
  24. Hammond, J., Le, Q., Goodyer, C., Gelfand, M., Trifiro, M., and LeBlanc, A. 2001. Testosterone-Mediated Neuroprotection Through the Androgen Receptor in Human Primary Neurons.J Neurochem. 77 (5): 1319-1326.
  25. Hooper, 1958. Lab 4 - Soft Anatomy: Rat Dissection. Available at: http://www.csus.edu/indiv/L/lancasterw/bio168/LABS%20BIO168-03/Lab5-soft%20anatomy%20BIO168-05.htmlBio168.
  26. Hsu, G.L., Wu Lin, C., Hsieh, C.H., Hsieh, J.T., Chen, C.S., Kuo, T.F, Ling, P.Y, Huang, H.M, Wang, C.J., and Tseng, G.F. 2005. Distal Ligament in Human Glans: A Comparative Study of Penile Architecture. Journal of Andrology. 26: 624-628.
  27. Ji-Kan Ryu., Dae-Jong K., Lee, T., Yun-Seog, K., Sang-Min, Y., and Jun-Kyu, S. 2003. The Role of Free Radical in the Pathogenesis of Impotence in Streptozotocin-Induced Diabetic Rats. Yonsei Medical Journal. 44 (2). 236-241.
  28. Kandeel, F.R., Koussa, V.K.T., Swerdloff, R.S. 2001. Male Sexual Function and Its Disorders: Physiology, Patophysiology, Clinical Investigation, and Treatment. Endocrine Reviews. 22 (3): 342-388.
  29. Kaufman, J.M. and Vermeulen, A. 2005. The Decline of Androgen Levels in Elderly Men and Its Clinical and Therapeutic Implications. Endocrine Reviews. 26: 833-876.
  30. Kellogg, D.L., Zhao, J.L., Friel, C., Roman, L.J. 2003. Nitric Oxide Concentration Increases in the Cutaneous Interstitial Space During Heat Stress in Humans. J Appl Physiol. 94: 1971-1977.
  31. Kelly, D.A. 2000. Anatomy of the Baculum-Corpus Cavernosum Interface in the Norway Rat (Rattus norvegicus), and Implications for Force Transfer During Copulation. Journal of Morphology. 244. 69-77.
  32. Knight, J.A., Pleper, R.K., and McClellan, L. 1988. Specificity of The Thiobarbituric Acid Reaction: Its Use in Studies of Lipid Peroxidation. Clin Chem 34 (12): 2433-2438.
  33. Lalamentik, G. 2008. Terapi Sulih Testosteron (Testosterone Replacement Therapy) Memperbaiki Korpus Kavernosum Tikus Wistar (Rattus Norvegicus) yang dikastrasi (tesis). Denpasar. Universitas Udayana.
  34. Leungwattanakij, S. Bivalacqua, T.J., Usta, M.F., Yang, D.Y., Hyun, J.S., Champion, H.C., Abdel-Mageed, A.B., and Hellstrom, W.J.G. 2003. Cavernous Neurotomy Causes Hypoxia and Fibrosis in Rat Corpus Cavernosum. J Androl. 24: 239-245.
  35. Liu, J.,Wang, X., Shigenaga, M.K., Yeo, H.C., Mori, A., Ames, B.N. 1996. Immobilization Stress Causes Oxidative Damage to Lipid, Protein, and DNA in the Brain Of Rats.. FASEB J. 10: 1532-1538.
  36. Lue, T., Giuliano, F., Khoury, S., Rosen, R. 2003. Clinical Manual of Sexual Medicine Sexual Dysfunctions in Men. Based on The Report of The 2 nd International Consultation on Sexual Dysfunctions.
  37. Lum, H., and Roebuck, K.A. 2001. Oxidant Stress and Endothelial Cell Dysfunction. Am J Physiol Cell. 280: C719-C741.
  38. Mayes, P.A., and Botham, K.M. 2003. Lipids of Physiologic Significance. In: Murray, R.K., Granner, D.K., Mayes, P.A., and Rodwel, V.W (editors). Harper’s Illustrated Biochemistry. 26th. Ed. New York: McGraw Hill. p. 111-121.
  39. McQuaid, K.E. and Keenan, A.K. 1997. Endothelial Barrier Dysfunction and Oxidative Stress: Roles for Nitric Oxide. Experimental Physiology. 82: 369-376.
  40. Monnier, L., Mas, E., Ginet, C., Michel, F., Villon, L., Cristol, J.P., and Colette, C. 2006. Acute Glucose Fluctuations Compared With Sustained Chronic Hyperglicemia in Patients With Type 2 Dibetes. JAMA. 295(14): 1681-1687.
  41. Moore, K.L., Dalley, A.F. 2006. Clinically Oriented Anatomy. 5th edition. Lippincott Williams & Wilkins. Philadelphia.
  42. Nishio, Y., Nakano, Y., Deguchi, Y., Terato, H., Ide, H., Ito, C., Ishida, H., Takagi, K., Tsuboi, H., Kinae, N., and Shimoi, K. 2007. Social Stress Induce Oxidative DNA Damage in Mouse Peripheral Blood Cells. Genes and Environment. 29; 17-22.
  43. Okruhlicova, L., Dlugosova, K., Mitasikova, M., Bernatova, I. 2006. Ultrastructural characteristics of aortic endothelial cells in borderline hypertensive rats exposed to chronic social stress. Physiological Research-Pre Press Article.
  44. Packer, L and Cadenas, L. 2008. Oxidative stress and Disease. In: Packer, L, and Sies, H (editors). Oxidative Stress and Inflammatory Mechanism in Obesity, Diabetes, and the Metabolic Syndrome. CRC Press. 12-16
  45. Panghiyangani, R. dan Suhartono, E. tt. Pengaruh Kontrasepsi Hormonal Pria Kombinasi Testosteron Enantat (TE) dan Depo Medroksi Progesteron Asetat (DMPA) Terhadap Pembentukan Radikal Bebas. Avaiable at: Http://Biologiweb.Files.Wordpress.Com/2008/10/Kontrasepsi-Te-Dmpa.Doc
  46. Pangkahila, W. 2001. Bahagia Tanpa Gangguan Fungsi Seksual. Cetakan ke-1. Jakarta: Penerbit Buku Kompas.
  47. Pangkahila, W. 2006. Disfungsi Ereksi. Cetakan ke-1. Jakarta: Ikatan Dokter Indonesia.
  48. Panjaitan, R.G.P., Handharyani, E., Chairul, Masriani, Zakiah, Z., and Manalu, W. 2007. Pengaruh Pemberian Karbon Tetraklorida Terhadap Fungsi Hati dan Ginjal Tikus. Makara Kesehatan. 11 (1): 11-16.
  49. Pham-Huy, L.A.P, He, H., and Pham-Huy, C. 2008. Free Radicals, Antioxidants in Disease and Health. Int J Biomed Sci. 4: 89-96.
  50. Pocock, S.J. 1984. The Size of Clinical Trial, In: Clinical Trials, A Practical Approach, John Wiley & Sons. 123-127.
  51. Rabin, D., Gold, P.W., Margioris, A.N., and Chrousos, G.P. 1986. Stress and Reproduction: Physiologic Interactions Between the Stress and Reproductive Axis. New York: Plenum Press.
  52. Rajasekaran, M., Hellstrom, W.J.G., and Sikka S.C. 2001. Nitric Oxide Induces Oxidative Stress and Mediates Cytotoxicity to Human Cavernosal Cells in Culture. Journal of Andrology. 22: 34-39.
  53. Randox CE Laboratories Ltd. 2006. RANSOD. 182-183.
  54. Sarkar, A. D., Maiti, R., and Ghosh, D. 2005. Induction of Oxidative Stress on Reproductive and Metabolic Organs in Sodium Fluoride-Treated Male Albino Rats: Protective Effect of Testosterone and Vitamin E Coadministration. Informa Healthcare. 15: 271-277.
  55. Sato, Y., Suzuki, N., Horita, H., Wada H., Shibuya, A., Adachi, H., Tsukamoto, T., Kumamoto, Y., and Yamamoto, M. 1996.
  56. Effects of Leong-term Psychological Stress on Sexual Behavior and Brain Catecholamine Levels. Journal of Andrology. 17 (2): 83-90.
  57. Singh, R., Artaza, J.N., Taylor, W.E., Gonzalez-Cadavid, N.F., Bhasin, S. 2003. Androgen Stimulate Myogenic Differentiation and Inhibit Adipogenesis in C3H 10T1/2 Pluripotent Cells Through an Androgen Receptor-Mediated Pathway. Endocrinology. 144: 5081-5088.
  58. Tam, N. T. C., Ying, G., Yuet-Kin, L., and Shuk-Mei, H. 2003.
  59. Androgen Regulation of Oxidative Stress in the Rat Prostat. American Journal of Pathology. 163: 2513-2522
  60. Terranova, P.F. 2000. The Male Reproductive System. In: Rhoades, R.A and Tanner, G.A., editors. Medical Physiology. Second edition. Oxford: Blackwell Synergy. p. 649-666.
  61. Tilbrook, A.J., Turner, A.I., and Clarke, I.J. 2000. Effects of Stress on Reproductive in Non-Rodent Mammals: The Role of Glucocorticoids and Sex Differences. Review of Reproduction. 5: 105-113.
  62. Traish, A.M., Goldstein, I., Kim, N.N. 2007. Testosterone and Erectile Function: From Basic Reasearch to a New Clinical Paradigm for Managing Men with Androgen Insufficiency and Erectile Dysfunction. Eur Urol. 52: 54-70.
  63. Traish, A.M., Munarriz, R., O’Connell, L., Choi, S. Kim, S.W., Kim, N.N., Huang, Y.H., Glodstein, I. 2003. Effects of Medical or Surgical Castration on Erectile Function in An Animal Model. Journal of Andrology, 24 (3): 381-387.
  64. Traish, A.M., Toselli, P., Jeong, S.J., Kim, N.N. 2005. Adipocyte Accumulation in Penile Corpus Cavernosum of the Orchiectomized Rabbit: a Potential Mechanism for Veno-occlusive Dysfunction in Androgen Deficiency. J Androl. 26: 242-248.
  65. Vinna, J., Gimeno, A., Sastre, J., Desco, C., Asesnsi, M., Pallardo, F.V., Cuesta, A., Ferrero, J.A., Terada, L.S., and Repine, J.E. 2000. Mechanism of Free Radical Production in Exhaustive Exercise in Humans and Rats; Role of Xanthine Oxidase and Protection by Allopurionol. Informa Healthcare. 49 (6): 539-544.
  66. Vinna, J., Gomez-Cabrera, M.C., Lioret, A., Marquez, R., Minana, J.B., Pallardo, F.V., and Sastre, J. 2001. Free Radical in Exhaustive Physical Exercise Mechanism of Production, and Protection by Antioksidants. Informa Healthcare. 50 (4): 271-277.
  67. Wardana, I.N.G. 2009a. Stres Psikososial Menyebabkan Terjadinya Stres Oksidatif pada Minggu Pertama Perlakuan. Penelitian Pendahuluan. Program Magister Ilmu Biomedik UNUD.
  68. Wardana, I.N.G. 2009b. Pemberian Injeksi Testosteron tidak Mampu Meredam Stres Oksidatif yang Terjadi pada Tikus yang Mendapatkan Stres Psikososial. Penelitian Pendahuluan. Program Magister Ilmu Biomedik UNUD.
  69. Wardana, I.N.G. 2009c. Pemberian Injeksi Testosteron Mempertahankan Jumlah Sel Otot Polos Korpus Kavernosum Penis Tikus. Penelitian Pendahuluan. Program Magister Ilmu Biomedik UNUD.
  70. Weissman, B.A., Sottas, C.M., Zhou, P., Iadecola, C., and Hardy, M.P. 2007. Testosterone Production in Mice Lacking Inducible Nitric Oxide Synthase Expression is Sensitive to Restraint Stress. Am J Physiol Endocrinol Metab. 292: E615-E620.
  71. Williams, P.L. 1995. Gray’s Anatomy. 38 th edition. Churchill Livingstone. Philadelphia
  72. Winarsi, H. 2007. Antioksidan Alami & Radikal Bebas. Penerbit Kanisius.
  73. Wink, D.A., Feelisch, M., Fukuto, J., Chistodoulou, D., Jourd'Heuil, D., Grisham, M.B., Vodovotz, Y., Cook, J.A., Krishna, M., DeGraff, W.G., Kim, S., Gamson, J., Mitchell, J.B. 1998. The Cytotoxicity of Nitroxyl: Possible Implications for the Pathophysiological Role of NO. Arch Biochem Biophys. 351: 66-74.
  74. Wresdiyanti, T., Astawan, M., Fithriani, D., Adnyane, K.M., Novelina, S., and Aryani, S. tt. Pengaruh α-Tokoferol Terhadap Profil Superoksida Dismutase dan Malondialdehida pada Jaringan Hati Tikus di Bawah Kondisi Stres. Jurnal Veteriner.
  75. Zirkin, B.R. and Chen, H. 2000. Regulation of Leydig Cell Steroidogenic Function During Aging. Biology of Reproduction. 63: 977-981.

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Wardana, I. N. G., Widianti, I., & Wirata, G. (2018). Testosterone increases corpus cavernous smooth muscle cells in oxidative stress-induced rodents (Sprague-Dawley). Bali Medical Journal, 7(2), 313–322. https://doi.org/10.15562/bmj.v7i2.970
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