Molecular and Cellular Biochemistry

, Volume 369, Issue 1–2, pp 195–204 | Cite as

Antioxidant treatment with edaravone or taurine ameliorates diabetes-induced testicular dysfunction in the rat

  • Panagiota Tsounapi
  • Motoaki Saito
  • Fotios Dimitriadis
  • Sotirios Koukos
  • Shogo Shimizu
  • Keisuke Satoh
  • Atsushi Takenaka
  • Nikolaos Sofikitis
Article

Abstract

Diabetes mellitus with the subsequent generation of reactive oxygen species represents a major risk factor for testicular dysfunction (TD). We investigate whether administration of antioxidants edaravone and taurine could prevent type 1 diabetes-induced TD in the rat. Six-week-old male Wistar rats were divided into four groups. Group A was treated with citrate–phosphate buffer plus normal saline, whereas in the other three groups, diabetes was induced by streptozotocin (50 mg/kg intraperitoneally). Subsequently, the diabetic rats were treated for 4 weeks either with normal saline (group B), edaravone (10 mg/Kg/day, intraperitoneally; group C), or taurine (500 mg/Kg/day, intraperitoneally; group D). Body, testicular, and epididymal weight, serum glucose, malondialdehyde levels, 8-Hydroxy-2’-deoxyguanosine(8-OH-dG) levels, testicular catalase activity, and serum testosterone levels were determined. Histological examination and the Johnsen score were used to observe and evaluate, respectively, the morphological changes in the testes. TUNEL assay was used to examine DNA fragmentation. Mating studies were performed in order to evaluate the fertility potential of male rats in each group. Edaravone or taurine treatment prevented significantly the decreased body, testicular, and epididymal weight induced by diabetes. Moreover, edaravone or taurine significantly decreased the diabetes-induced malondialdehyde levels, 8-OHdG levels, the morphological damage, and the number of apoptotic cells. Taurine, but not edaravone, increased significantly the testicular catalase activity. The antioxidant treatment had no effect on the fertility potential of the diabetic rats. The morphological damage, increased lipid peroxidation, and apoptosis in testicular tissue can be significantly relieved by edaravone or taurine treatment through suppressing the increased oxidative stress in the rat testis.

Keywords

Antioxidants Edaravone Taurine Diabetes mellitus Reactive oxygen species (ROS) Oxidative stress Testicular dysfunction 

References

  1. 1.
    Dahlquist G, Kallen B (2005) Mortality in childhood-onset type 1 diabetes: a population-based study. Diabetes Care 28:2384–2387PubMedCrossRefGoogle Scholar
  2. 2.
    Agbaje IM, Rogers DA, McVicar CM, McClure N, Atkinson AB, Mallidis C, Lewis SE (2007) Insulin dependant diabetes mellitus: implications for male reproductive function. Hum Reprod 22:1871–1877PubMedCrossRefGoogle Scholar
  3. 3.
    Amaral S, Oliveira PJ, Ramalho-Santos J (2008) Diabetes and the impairment of reproductive function: possible role of mitochondria and reactive oxygen species. Curr Diabetes Rev 4:46–54PubMedCrossRefGoogle Scholar
  4. 4.
    Cai L, Chen S, Evans T, Deng DX, Mukherjee K, Chakrabarti S (2000) Apoptotic germ-cell death and testicular damage in experimental diabetes: prevention by endothelin antagonism. Urol Res 28:342–347PubMedCrossRefGoogle Scholar
  5. 5.
    Koh PO (2007) Streptozotocin-induced diabetes increases the interaction of Bad/Bcl-XL and decreases the binding of pBad/14-3-3 in rat testis. Life Sci 81:1079–1084PubMedCrossRefGoogle Scholar
  6. 6.
    Mallidis C, Agbaje I, O’Neill J, McClure N (2009) The influence of type 1 diabetes mellitus on spermatogenic gene expression. Fertil Steril 92:2085–2087PubMedCrossRefGoogle Scholar
  7. 7.
    Zhao H, Xu S, Wang Z, Li Y, Guo W, Lin C, Gong S, Li C, Wang G, Cai L (2010) Repetitive exposures to low-dose X-rays attenuate testicular apoptotic cell death in streptozotocin-induced diabetes rats. Toxicol Lett 192:356–364PubMedCrossRefGoogle Scholar
  8. 8.
    Zhao Y, Tan Y, Dai J, Li B, Guo L, Cui J, Wang G, Shi X, Zhang X, Mellen N, Li W, Cai L (2011) Exacerbation of diabetes-induced testicular apoptosis by zinc deficiency is most likely associated with oxidative stress, p38 MAPK activation, and p53 activation in mice. Toxicol Lett 200(1–2):100–106PubMedCrossRefGoogle Scholar
  9. 9.
    Navarro-Casado L, Juncos-Tobarra MA, Chafer-Rudilla M, de Onzono LI, Blazquez-Cabrera JA, Miralles-Garcia JM (2010) Effect of experimental diabetes and STZ on male fertility capacity. Study in rats. J Androl 31:584–592PubMedCrossRefGoogle Scholar
  10. 10.
    Soudamani S, Yuvaraj S, Malini T, Balasubramanian K (2005) Experimental diabetes has adverse effects on the differentiation of ventral prostate during sexual maturation of rats. Anat Rec A Discov Mol Cell Evol Biol 287:1281–1289PubMedGoogle Scholar
  11. 11.
    Scarano WR, Messias AG, Oliva SU, Klinefelter GR, Kempinas WG (2006) Sexual behaviour, sperm quantity and quality after short-term streptozotocin-induced hyperglycaemia in rats. Int J Androl 29:482–488PubMedCrossRefGoogle Scholar
  12. 12.
    Baccetti B, La Marca A, Piomboni P, Capitani S, Bruni E, Petraglia F, De Leo V (2002) Insulin-dependent diabetes in men is associated with hypothalamo-pituitary derangement and with impairment in semen quality. Hum Reprod 17:2673–2677PubMedCrossRefGoogle Scholar
  13. 13.
    Maatman TJ, Montague DK, Martin LM (1987) Erectile dysfunction in men with diabetes mellitus. Urology 29:589–592PubMedCrossRefGoogle Scholar
  14. 14.
    Zanardo RC, Costa Cruz JW, Oliveira MA, Fortes ZB (2003) Ascorbic acid supplementation restores defective leukocyte-endothelial interaction in alloxan-diabetic rats. Diabetes Metab Res Rev 19:60–68PubMedCrossRefGoogle Scholar
  15. 15.
    Armagan A, Uz E, Yilmaz HR, Soyupek S, Oksay T, Ozcelik N (2006) Effects of melatonin on lipid peroxidation and antioxidant enzymes in streptozotocin-induced diabetic rat testis. Asian J Androl 8:595–600PubMedCrossRefGoogle Scholar
  16. 16.
    Aybek H, Aybek Z, Rota S, Sen N, Akbulut M (2008) The effects of diabetes mellitus, age, and vitamin E on testicular oxidative stress. Fertil Steril 90:755–760PubMedCrossRefGoogle Scholar
  17. 17.
    Palmeira CM, Santos DL, Seica R, Moreno AJ, Santos MS (2001) Enhanced mitochondrial testicular antioxidant capacity in Goto-Kakizaki diabetic rats: role of coenzyme Q. Am J Physiol Cell Physiol 281:C1023–C1028PubMedGoogle Scholar
  18. 18.
    Anuradha CV (2009) Aminoacid support in the prevention of diabetes and diabetic complications. Curr Protein Pept Sci 10:8–17PubMedCrossRefGoogle Scholar
  19. 19.
    Schaffer SW, Azuma J, Mozaffari M (2009) Role of antioxidant activity of taurine in diabetes. Can J Physiol Pharmacol 87:91–99PubMedCrossRefGoogle Scholar
  20. 20.
    Watanabe K, Morinaka Y, Iseki K, Watanabe T, Yuki S, Nishi H (2003) Structure-activity relationship of 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone). Redox Rep 8:151–155PubMedCrossRefGoogle Scholar
  21. 21.
    Saito M, Kinoshita Y, Satoh I, Shinbori C, Suzuki H, Yamada M, Watanabe T, Satoh K (2007) Ability of cyclohexenonic long-chain fatty alcohol to reverse diabetes-induced cystopathy in the rat. Eur Urol 51:479–487 discussion 487–8PubMedCrossRefGoogle Scholar
  22. 22.
    Tamamura M, Saito M, Kinoshita Y, Shimizu S, Satoh I, Shomori K, Dimitriadis F, Satoh K (2010) Protective effect of edaravone, a free-radical scavenger, on ischaemia-reperfusion injury in the rat testis. BJU Int 105:870–876PubMedCrossRefGoogle Scholar
  23. 23.
    Johnsen SG (1970) Testicular biopsy score count: a method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males. Hormones 1:2–25PubMedCrossRefGoogle Scholar
  24. 24.
    Amaral S, Moreno AJ, Santos MS, Seica R, Ramalho-Santos J (2006) Effects of hyperglycemia on sperm and testicular cells of Goto-Kakizaki and streptozotocin-treated rat models for diabetes. Theriogenology 66:2056–2067PubMedCrossRefGoogle Scholar
  25. 25.
    Shrilatha B (2007) Occurrence of oxidative impairments, response of antioxidant defences and associated biochemical perturbations in male reproductive milieu in the Streptozotocin-diabetic rat. Int J Androl 30:508–518PubMedCrossRefGoogle Scholar
  26. 26.
    Shrilatha B, Muralidhara (2007) Early oxidative stress in testis and epididymal sperm in streptozotocin-induced diabetic mice: its progression and genotoxic consequences. Reprod Toxicol 23:578–587PubMedCrossRefGoogle Scholar
  27. 27.
    Agarwal A, Said TM (2005) Oxidative stress, DNA damage and apoptosis in male infertility: a clinical approach. BJU Int 95:503–507PubMedCrossRefGoogle Scholar
  28. 28.
    Naziroglu M (2003) Enhanced testicular antioxidant capacity in streptozotocin-induced diabetic rats: protective role of vitamins C and E and selenium. Biol Trace Elem Res 94:61–72PubMedCrossRefGoogle Scholar
  29. 29.
    Pigeolet E, Corbisier P, Houbion A, Lambert D, Michiels C, Raes M, Zachary MD, Remacle J (1990) Glutathione peroxidase, superoxide dismutase, and catalase inactivation by peroxides and oxygen derived free radicals. Mech Ageing Dev 51:283–297PubMedCrossRefGoogle Scholar
  30. 30.
    Paz G, Homonnai ZT (1979) Leydig cell function in streptozotocin-induced diabetic rats. Experientia 35:1412–1413PubMedCrossRefGoogle Scholar
  31. 31.
    Sexton WJ, Jarow JP (1997) Effect of diabetes mellitus upon male reproductive function. Urology 49:508–513PubMedCrossRefGoogle Scholar
  32. 32.
    Orth JM, Murray FT, Bardin CW (1979) Ultrastructural changes in Leydig cells of streptozotocin-induced diabetic rats. Anat Rec 195:415–430PubMedCrossRefGoogle Scholar
  33. 33.
    Cummins JM, Jequier AM, Kan R (1994) Molecular biology of human male infertility: links with aging, mitochondrial genetics, and oxidative stress? Mol Reprod Dev 37:345–362PubMedCrossRefGoogle Scholar
  34. 34.
    Sikka SC (2001) Relative impact of oxidative stress on male reproductive function. Curr Med Chem 8:851–862PubMedGoogle Scholar
  35. 35.
    Aitken RJ, Sawyer D (2003) The human spermatozoon: not waving but drowning. Adv Exp Med Biol 518:85–98PubMedCrossRefGoogle Scholar
  36. 36.
    Sinha Hikim AP, Swerdloff RS (1999) Hormonal and genetic control of germ cell apoptosis in the testis. Rev Reprod 4:38–47PubMedCrossRefGoogle Scholar
  37. 37.
    Aitken RJ, Harkiss D, Buckingham D (1993) Relationship between iron-catalysed lipid peroxidation potential and human sperm function. J Reprod Fertil 98:257–265PubMedCrossRefGoogle Scholar
  38. 38.
    Diemer T, Allen JA, Hales KH, Hales DB (2003) Reactive oxygen disrupts mitochondria in MA-10 tumor Leydig cells and inhibits steroidogenic acute regulatory (StAR) protein and steroidogenesis. Endocrinology 144:2882–2891PubMedCrossRefGoogle Scholar
  39. 39.
    Doreswamy K, Shrilatha B, Rajeshkumar T, Muralidhara (2004) Nickel-induced oxidative stress in testis of mice: evidence of DNA damage and genotoxic effects. J Androl 25:996–1003PubMedGoogle Scholar
  40. 40.
    Murata M, Takahashi A, Saito I, Kawanishi S (1999) Site-specific DNA methylation and apoptosis: induction by diabetogenic streptozotocin. Biochem Pharmacol 57:881–887PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Panagiota Tsounapi
    • 1
    • 2
  • Motoaki Saito
    • 2
  • Fotios Dimitriadis
    • 2
    • 3
  • Sotirios Koukos
    • 4
  • Shogo Shimizu
    • 2
  • Keisuke Satoh
    • 2
  • Atsushi Takenaka
    • 1
  • Nikolaos Sofikitis
    • 4
  1. 1.Division of Urology, Department of SurgeryTottori University School of MedicineYonagoJapan
  2. 2.Division of Molecular Pharmacology, Department of Pathophysiological and Therapeutic ScienceTottori University School of MedicineYonagoJapan
  3. 3.2nd Department of Urology, Papageorgiou HospitalAristotle University of ThessalonikiThessalonikiGreece
  4. 4.Laboratory of Molecular Urology and Genetics of Human Reproduction, Department of UrologyIoannina University School of MedicineIoanninaGreece

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