Skip to main content
Log in

Effect of Oral Zinc Supplementation on the Thiol Oxido-Reductive Index and Thiol-Related Enzymes in Seminal Plasma and Spermatozoa of Iraqi Asthenospermic Patients

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

A thiol group plays an essential role in sperm metabolism and the antioxidative defense state. Zinc is the second most abundant element in the human body, following iron. The present study was conducted to study the effect of zinc supplementation on the characteristics of semen along with thiol and thiol-related enzymes in semen of asthenospermic patients. Semen samples were obtained from 60 fertile and 60 asthenospermic men, from couples who had consulted the infertility clinic of Babil Hospital (Hillah city, Iraq). The subfertile group was treated with zinc; every participant took two 220 mg capsules of zinc sulfate per day for 3 months. Semen samples were obtained (before and after zinc supplementation). The levels of reduced thiol, oxidized thiol, thiol oxido-reductive index, and thiol-related enzymes activities were determined in spermatozoa and seminal plasma of patients and healthy groups. Oxidized thiol levels were significantly higher in the infertile patients compared to that in the fertile group. Conversely, reduced thiol level, sulfhydryl oxidase activity, and glutathione peroxidase activity significantly decreased in the infertile patients compared to that in the fertile group. Oxidized thiol levels, reduced thiol levels, and thiol-related enzymes activities of the infertile patients were restored to normal values after treatment with zinc. However, reduced and oxidized thiol levels in spermatozoa did not change significantly in the group treated with zinc. The quantitative values for RSH/RSSR and thiol-related enzymes may provide useful means to qualitatively express the oxidant/antioxidant balance in clinical and epidemiologic studies. ClinicalTrials.gov Identifier: NCT02985905

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

GSSG:

Oxidized glutathione

C.I.:

Confidence interval for mean

GSH:

Reduced glutathione

MTs:

Metallothioneins

Se-GPx:

Selenium-dependent glutathione peroxidase

SHO:

sulfhydryl oxidase

RSSR:

Oxidized thiol

RSH:

Reduced thiol

RSH/RSSR:

Thiol oxido-reductive index

GPx:

Glutathione peroxidase

non-Se-GPx:

non-selenium-dependent glutathione peroxidase

ROS:

Reactive oxygen species

WHO:

World Health Organization

References

  1. Shukla KK, Mahdi AA, Mishra V, Rajender S, Sankhwar SN, Patel D, Das M (2011) Withania somnifera improves semen quality by combating oxidative stress and cell death and improving essential metal concentrations. Reprod BioMed Online 22(5):421–427. https://doi.org/10.1016/j.rbmo.2011.01.010

    Article  PubMed  Google Scholar 

  2. Halliwell B (2001) Free radicals and other reactive species in disease, Encyclopedia of Life Sciences. Nature Publishing Group / www.els.net (pp: 1–7)

  3. Simoni M, Tüttelmann F, Gromoll J, Nieschlag E (2008) Clinical consequences of microdeletions of the Y chromosome: the extended Münster experience. Reprod BioMed Online 16(2):289–303. https://doi.org/10.1016/S1472-6483(10)60588-3

    Article  CAS  PubMed  Google Scholar 

  4. Esteves SC, Agarwal A (2011) Novel concepts in male infertility. Int Braz J Urol 37(1):5–15

    Article  PubMed  Google Scholar 

  5. El-Tohamy MM (2012) The mechanisms by which oxidative stress and free radical damage produces male infertility. Life Sci J 9(1):674–688

    Google Scholar 

  6. El-Taieb MA, Herwig R, Nada EA, Greilberger J, Marberger M (2009) Oxidative stress and epididymal sperm transport, motility and morphological defects. Eur J Obstet Gynecol Reprod Biol 144:S199–S203. https://doi.org/10.1016/j.ejogrb.2009.02.018

    Article  CAS  PubMed  Google Scholar 

  7. Castegna A, Drake J, Pocernich C, Butterfield DA (2003) Protein carbonyl levels—an assessment of protein oxidation. Methods in biological oxidative Stress. pp161-pp168

  8. Hadwan MH, Almashhedy LA, Alsalman AR (2014) Study of the effects of oral zinc supplementation on peroxynitrite levels, arginase activity and NO synthase activity in seminal plasma of Iraqi asthenospermic patients. Reprod Biol Endocrinol 12(1):1

    Article  PubMed  PubMed Central  Google Scholar 

  9. Cabrillana ME, Uribe P, Villegas JV, Álvarez J, Sánchez R, Fornés MW (2016) Thiol oxidation by nitrosative stress: cellular localization in human spermatozoa. Syst Biol Reprod Med 62(5):325–334. https://doi.org/10.1080/19396368.2016.1208782

    Article  CAS  PubMed  Google Scholar 

  10. Anghel A, Zamfirescu S, Coprean D, Sogorescu E (2009) Annals of the Romanian Society for Cell. Biology 14:97–103

    Google Scholar 

  11. Cornwall GA, Vindivich D, Tillman S, Chang TS (1988) The effect of sulfhydryl oxidation on the morphology of immature hamster epididymal spermatozoa induced to acquire motility in vitro. Biol Reprod 39(1):141–155

    Article  CAS  PubMed  Google Scholar 

  12. Buettner GR (1993) The pecking order of free radicals and antioxidants: lipid peroxidation, α-tocopherol, and ascorbate. Arch Biochem Biophys 300(2):535–543. https://doi.org/10.1006/abbi.1993.1074

    Article  CAS  PubMed  Google Scholar 

  13. Jain SK (1989) Hyperglycemia can cause membrane lipid peroxidation and osmotic fragility in human red blood cells. J Biol Chem 264(35):21340–21345

    CAS  PubMed  Google Scholar 

  14. Hamid AA, Aiyelaagbe OO, Usman LA, Ameen OM, Lawal A (2010) Antioxidants: its medicinal and pharmacological applications. Afr J Pure Appl Chem 4(8):142–151

    CAS  Google Scholar 

  15. Chabory E, Damon C, Lenoir A, Henry-Berger J, Vernet P, Cadet R, Saez F, Drevet JR (2010) Mammalian glutathione peroxidases control acquisition and maintenance of spermatozoa integrity. J Anim Sci 88(4):1321–1331. https://doi.org/10.2527/jas.2009-2583

    Article  CAS  PubMed  Google Scholar 

  16. Nordberg J, Arner ES (2001) Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radic Biol Med 31(11):1287–1312. https://doi.org/10.1016/S0891-5849(01)00724-9

    Article  CAS  PubMed  Google Scholar 

  17. Alvarez JG, Storey BT (1989) Role of glutathione peroxidase in protecting mammalian spermatozoa from loss of motility caused by spontaneous lipid peroxidation. Gamete Res 23(1):77–90. https://doi.org/10.1002/mrd.1120230108

    Article  CAS  PubMed  Google Scholar 

  18. Foresta C, Flohé L, Garolla A, Roveri A, Ursini F, Maiorino M (2002) Male fertility is linked to the selenoprotein phospholipid hydroperoxide glutathione peroxidase. Biol Reprod 67(3):967–971. https://doi.org/10.1095/biolreprod.102.003822

    Article  CAS  PubMed  Google Scholar 

  19. Faccio G, Kruus K, Buchert J, Saloheimo M (2010) Secreted fungal sulfhydryl oxidases: sequence analysis and characterisation of a representative flavin-dependent enzyme from Aspergillus oryzae. BMC Biochem 11(1):1

    Article  Google Scholar 

  20. Chimienti F, Aouffen M, Favier A, Seve M (2003) Zinc homeostasis-regulating proteins: new drug targets for triggering cell fate. Curr Drug Targets 4(4):323–338. https://doi.org/10.2174/1389450033491082

    Article  CAS  PubMed  Google Scholar 

  21. Hadwan MH, Almashhedy LA, Alsalman AR (2015) Oral zinc supplementation restores superoxide radical scavengers to normal levels in spermatozoa of Iraqi asthenospermic patients. Int J Vitam Nutr Res 85(3–4):165–173. https://doi.org/10.1024/0300-9831/a000235

    Article  CAS  PubMed  Google Scholar 

  22. Mocchegiani E, Costarelli L, Giacconi R, Cipriano C, Muti E, Malavolta M (2006) Zinc-binding proteins (metallothionein and α-2 macroglobulin) and immunosenescence. Exp Gerontol 41(11):1094–1107. https://doi.org/10.1016/j.exger.2006.08.010

    Article  CAS  PubMed  Google Scholar 

  23. Hadwan MH, Almashhedy LA, Alsalman AR (2012) Oral zinc supplementation restore high molecular weight seminal zinc binding protein to normal value in Iraqi infertile men. BMC Urol 12(1):32. https://doi.org/10.1186/1471-2490-12-32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. (WHO) World Health Organization (2010) WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction, 5th edn. Cambridge University Press, Cambridge

    Google Scholar 

  25. Riddles PW, Blakeley RL, Zerner B (1983) Reassessment of Ellman’s reagent. Methods Enzymol 91:49–60. https://doi.org/10.1016/S0076-6879(83)91010-8

    Article  CAS  PubMed  Google Scholar 

  26. Tannhauser TW, Konishi Y, Sheraga HA (1984) Sensitive quantitative analysis of disulfide bond in polypeptides and proteins. Anal Biochem 138(1):181–188. https://doi.org/10.1016/0003-2697(84)90786-3

    Article  Google Scholar 

  27. Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra W (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science 179(4073):588–590. https://doi.org/10.1126/science.179.4073.588

    Article  CAS  PubMed  Google Scholar 

  28. Hadwan MH, Almashhedy LA, Alsalman AS (2014) BioTechnol: Indian J 9:376–382

    CAS  Google Scholar 

  29. Hadwan MH (2008) The activities of catalase in the spermatozoa and seminal plasma of patients with asthenospermia; and their relationship with oxidants and antioxidants. Iraqi Natl J Chem 31:514–521

    Google Scholar 

  30. Eskiocak S, Gozen AS, Yapar SB, Tavas F, Kilic AS, Eskiocak M (2005) Glutathione and free sulphydryl content of seminal plasma in healthy medical students during and after exam stress. Hum Reprod 20(9):2595–2600. https://doi.org/10.1093/humrep/dei062

    Article  CAS  PubMed  Google Scholar 

  31. Yoganathan T, Eskild W, Hansson V (1989) Investigation of detoxification capacity of rat testicular germ cells and Sertoli cells. Free Radic Biol Med 7(4):355–359. https://doi.org/10.1016/0891-5849(89)90121-4

    Article  CAS  PubMed  Google Scholar 

  32. Yoganathan T, Oyen O, Eskild W, Jahnsen T, Hansson V (1989) Cellular localization and age dependent changes in mRNA for glutathione S-transferase-P in rat testicular cells. Biochem Int 19(4):667–672

    CAS  PubMed  Google Scholar 

  33. Li TK (1975) The glutathione and thiol content of mammalian spermatozoa and seminal plasma. Biol Reprod 12(5):641–646. https://doi.org/10.1095/biolreprod12.5.641

    Article  CAS  PubMed  Google Scholar 

  34. Daunter B, Hill R, Hennessey J, Mackay EV (1981) Seminal plasma biochemistry I. Andrologia 13(2):131–141

    Article  CAS  PubMed  Google Scholar 

  35. Yeung CH, Cooper TG, De Geyter M, De Geyter C, Rolf C, Kamischke A (1998) Nieschlag E. Studies on the origin of redox enzymes in seminal plasma and their relationship with results of in-vitro fertilization. Mol Hum Reprod 4(9):835–839. https://doi.org/10.1093/molehr/4.9.835

    Article  CAS  PubMed  Google Scholar 

  36. Atig F, Raffa M, Habib BA, Kerkeni A, Saad A, Ajina M (2012) Impact of seminal trace element and glutathione levels on semen quality of Tunisian infertile men. BMC Urol 12(1):1

    Article  Google Scholar 

  37. Nikodemus D, Lazic D, Bach M, Bauer T, Pfeiffer C, Wiltzer L, Lain E, Schömig E, Gründemann D (2011) Paramount levels of ergothioneine transporter SLC22A4 mRNA in boar seminal vesicles and cross-species analysis of ergothioneine and glutathione in seminal plasma. J Physiol Pharmacol 62(4):411–419

    CAS  PubMed  Google Scholar 

  38. Anghel A, Zamfirescu S, Coprean D, Sogorescu E (2009) The effects of cystein, bovine serum albumin and vitamin E on the calitative parameters of frozen-thawed ram semen. Ann Rom Soc Cell Biol 14(2)

  39. Hadwan MH, Jabber FA, Tarish AH (2009) Zinc, copper, and superoxide dismutase in spermatozoa of patients with asthenospermia. Kerbala J Med 2:420–429

    Google Scholar 

  40. Reed DJ (1990) Status of calcium and thiols in hepatocellular injury by oxidative stress. In seminars in liver disease Vol. 10, No. 04, Thieme Medical Publishers, pp. 285–292

  41. Grankvist K, Marklund SL, Täljedal IB (1981) CuZn-superoxide dismutase, Mn-superoxide dismutase, catalase and glutathione peroxidase in pancreatic islets and other tissues in the mouse. Biochem J 199(2):393–398. https://doi.org/10.1042/bj1990393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Blum J, Fridovich I (1985) Inactivation of glutathione peroxidase by superoxide radical. Arch Biochem Biophys 240(2):500–508. https://doi.org/10.1016/0003-9861(85)90056-6

    Article  CAS  PubMed  Google Scholar 

  43. Ge YF, Wang CH, Ouyang LX, Shao Y, Yao B, Xia XY, Shang XJ, Huang YF (2008) Determination of plasma homocysteine in oligospermia and/or asthenospermia patients Zhonghua nan ke xue=. Natl J Androl 14(12):1112–1114

    CAS  Google Scholar 

  44. Upchurch GR, Welch GN, Fabian AJ, Freedman JE, Johnson JL, Keaney JF, Loscalzo J (1997) Homocyst (e) ine decreases bioavailable nitric oxide by a mechanism involving glutathione peroxidase. J Biol Chem 272(27):17012–17017. https://doi.org/10.1074/jbc.272.27.17012

    Article  CAS  PubMed  Google Scholar 

  45. Moslemi MK, Tavanbakhsh S (2011) Selenium–vitamin E supplementation in infertile men: effects on semen parameters and pregnancy rate. Int J Gen Med 4:99

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. You ZL, Shi DH, Zhu HL (2006) The inhibition of xanthine oxidase by the Schiff base zinc (II) complex. Inorg Chem Commun 9(6):642–644. https://doi.org/10.1016/j.inoche.2006.03.023

    Article  CAS  Google Scholar 

  47. Omu AE, Oahti H, Al-Othman S (1998) Treatment of asthenozoospermia with zinc sulphate: andrological, immunologieal and obstetric outcome. Eur J Obstet Gynaecol Reprod Biol 79(2):179–184. https://doi.org/10.1016/S0301-2115(97)00262-5

    Article  CAS  Google Scholar 

  48. Omu AE, Al-Azemi MK, Kehinde EO (2008) Indication of the mechanisms involved in improved sperm parameters by zinc therapy. Med Princ Pract 17(2):108–116. https://doi.org/10.1159/000112963

    Article  CAS  PubMed  Google Scholar 

  49. Wong WY, Merkus HM, Thomas CMG (2002) Effects of folic acid and zinc sulfate on male factor subfertlity: a double-blind, randomized, placebo-controlled trial. Fertil Steril 77(3):491–498. https://doi.org/10.1016/S0015-0282(01)03229-0

    Article  PubMed  Google Scholar 

  50. Reyes A, Mercado E, Goicoechea B, Rosado A (1976) Participation of membrane sulfhydryl groups in the epididymal maturation of human and rabbit spermatozoa. Fertil Steril 27(12):1452–1458. https://doi.org/10.1016/S0015-0282(16)42263-6

    Article  CAS  PubMed  Google Scholar 

  51. Cornwall GA, Vindivich D, Tillman S, Chang TS (1988) The effect of sulfhydryl oxidation on the morphology of immature hamster epididymal spermatozoa induced to acquire motility in vitro. Biol Reprod 39(1):141–155. https://doi.org/10.1095/biolreprod39.1.141

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We want to thank all researchers of the Chemistry Department (College of Science, University of Babylon, Hilla, Iraq) for their help and assistance during chemical analysis.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mahmoud Hussein Hadwan.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

Ethical Committee

Iraq: Ethics Committee (University of Babylon/College of Science), Reference number of approval: 545; Date: 22/6/2011.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Alsalman, A.R.S., Almashhedy, L.A. & Hadwan, M.H. Effect of Oral Zinc Supplementation on the Thiol Oxido-Reductive Index and Thiol-Related Enzymes in Seminal Plasma and Spermatozoa of Iraqi Asthenospermic Patients. Biol Trace Elem Res 184, 340–349 (2018). https://doi.org/10.1007/s12011-017-1215-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-017-1215-8

Keywords

Navigation