Biological Trace Element Research

, Volume 185, Issue 1, pp 106–115 | Cite as

Cadmium Testicular Toxicity in Male Wistar Rats: Protective Roles of Zinc and Magnesium

  • Nasim Babaknejad
  • Somaye Bahrami
  • Ali Asghar Moshtaghie
  • Hashem NayeriEmail author
  • Parvin Rajabi
  • Farhad Golshan Iranpour


Cadmium (Cd) is a highly toxic element, which may cause toxicity to most organs in the body. Zinc (Zn) and magnesium (Mg) are essential minerals with probable benefits on Cd harmful effects. Finding an efficient and non-pathological treatment against Cd toxicity seems promising. Fifty adult rats were divided into ten experimental groups of five rats each. The Cd group was treated with 1 mg Cd/kg and the control group received 0.5 cm3 normal saline. The other eight groups received Zn (0.5 and 1.5 mg/kg) and Mg (0.5 and 1.5 mg/kg) either alone or in combination with 1 mg Cd/kg through IP injection for 3 weeks. Testis malondialdehyde (MDA), sperm parameters, and testis histopathology were investigated. Cd reduced sperm parameters and increased testis MDA. Moreover, Cd exposure caused a significant histological damage in testis of male rats. However, Zn or Mg treatment prevented and reversed Cd toxic alterations in testis. These findings suggest that co-administration of Zn or Mg could improve cadmium testicular toxicity in male Wistar rats.


Cadmium Testicular toxicity Zinc Magnesium 


Authors’ Contributions

All authors participated in the writing of this paper.

Compliance with Ethical Standards

The study was approved by Isfahan University of Medical Science Experimental Animals Local Ethics Committee

Conflict of Interest

The authors declare that they have no competing interests.


  1. 1.
    Zegers-Hochschild F, Adamson GD, de Mouzon J, Ishihara O, Mansour R, Nygren K, Sullivan E, Vanderpoel S (2009) International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary of ART terminology, 2009. Fertil Steril 92(5):1520–1524. CrossRefPubMedGoogle Scholar
  2. 2.
    Feng HL (2003) Molecular biology of male infertility. Arch Androl 49:19–27CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Sharma R, Biedenharn KR, Fedor JM, Agarwal A (2013) Lifestyle factors and reproductive health: taking control of your fertility. Reprod Biol Endocrinol 11(1):66. CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Wong EW, Cheng CY (2011) Impacts of environmental toxicants on male reproductive dysfunction. Trends Pharmacol Sci 32(5):290–299. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Meeker JD, Rossano MG, Protas B, Diamond MP, Puscheck E, Daly D, Paneth N, Wirth JJ (2008) Cadmium, lead, and other metals in relation to semen quality: human evidence for molybdenum as a male reproductive toxicant. Environ Health Perspect 116(11):1473–1479. CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Siu ER, Mruk DD, Porto CS, Cheng CY (2009) Cadmium-induced testicular injury. Toxicol Appl Pharmacol 238(3):240–249. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Laskey JW, Rehnberg GL, Laws SC, Hein JF (1984) Reproductive effects of low acute doses of cadmium chloride in adult male rats. Toxicol Appl Pharmacol 73(2):250–255. CrossRefPubMedGoogle Scholar
  8. 8.
    Amara S, Abdelmelek H, Garrel C, Guiraud P, Douki T, Ravanat JL et al (2008) Preventive effect of zinc against cadmium-induced oxidative stress in the rat testis. J Reprod Dev 54(2):129–134. CrossRefPubMedGoogle Scholar
  9. 9.
    Benoff S, Hauser R, Marmar JL, Hurley IR, Napolitano B, Centola GM (2009) Cadmium concentrations in blood and seminal plasma: correlations with sperm number and motility in three male populations (infertility patients, artificial insemination donors, and unselected volunteers). Mol Med 15(7-8):248–262. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    He L, Wang B, Hay EB, Nebert DW (2009) Discovery of ZIP transporters that participate in cadmium damage to testis and kidney. Toxicol Appl Pharmacol 238(3):250–257. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Al-Azemi M, Omu FE, Kehinde EO, Anim JT, Oriowo MA, Omu AE (2010) Lithium protects against toxic effects of cadmium in the rat testes. J Assist Reprod Genet 27(8):469–476. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    El-Demerdash FM, Yousef MI, Kedwany FS, Baghdadi HH (2004) Cadmium-induced changes in lipid peroxidation, blood hematology, biochemical parameters and semen quality of male rats: protective role of vitamin E and beta-carotene. Food Chem Toxicol 42(10):1563–1571. CrossRefPubMedGoogle Scholar
  13. 13.
    Wong WY, Flik G, Groenen PM, Swinkels DW, Thomas CM, Copius-Peereboom JH et al (2001) The impact of calcium, magnesium, zinc, and copper in blood and seminal plasma on semen parameters in men. Reprod Toxicol 15(2):131–136. CrossRefPubMedGoogle Scholar
  14. 14.
    Wu SH, Oldfield JE, Whanger PD, Weswig PH (1973) Effect of selenium, vitamin E, and antioxidants on testicular function in rats. Biol Reprod 8:625–629CrossRefPubMedGoogle Scholar
  15. 15.
    Matovic V, Bulat ZP, Djukic-cosic D, Soldatovic D (2010) Zinc, copper, or magnesium supplementation against cadmium toxicity. Nova Science Publishers, UKGoogle Scholar
  16. 16.
    Chasapis CT, Loutsidou AC, Spiliopoulou CA, Stefanidou ME (2012) Zinc and human health: an update. Arch Toxicol 86(4):521–534. CrossRefPubMedGoogle Scholar
  17. 17.
    Zhao J, Dong X, Hu X, Long Z, Wang L, Liu Q, Sun B, Wang Q, Wu Q, Li L (2016) Zinc levels in seminal plasma and their correlation with male infertility: a systematic review and meta-analysis. Sci Rep 6(1):22386. CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Bonda E, Wlostowski T, Krasowska A (2004) Testicular toxicity induced by dietary cadmium is associated with decreased testicular zinc and increased hepatic and renal metallothionein and zinc in the bank vole (Clethrionomys glareolus). Biometals 17(6):615–624. CrossRefPubMedGoogle Scholar
  19. 19.
    Rafique M, Pervez S, Tahir F (2010) Protective effect of zinc over lead toxicity on testes. J Coll Physicians Surg Pak 20:377–381PubMedGoogle Scholar
  20. 20.
    Ahmadi S, Bashiri R, Ghadiri-Anari A, Nadjarzadeh A (2016) Antioxidant supplements and semen parameters: an evidence based review. Int J Reprod Biomed 14:729–736CrossRefGoogle Scholar
  21. 21.
    Theophanides T, Anastssopoulou J (1997) Magnesium: current status and new developments. Springer, Netherlands. CrossRefGoogle Scholar
  22. 22.
    Jacobs RM, Jones AO, Fox MR, Lener J (1983) Effects of dietary zinc, manganese, and copper on tissue accumulation of cadmium by Japanese quail. Proc Soc Exp Biol Med 172:34–38CrossRefPubMedGoogle Scholar
  23. 23.
    Noel L, Huynh-Delerme C, Guerin T, Huet H, Fremy JM, Kolf-Clauw M (2006) Cadmium accumulation and interactions with zinc, copper, and manganese, analysed by ICP-MS in a long-term Caco-2 TC7 cell model. Biometals 19(5):473–481. CrossRefPubMedGoogle Scholar
  24. 24.
    Matovic V, Plamenac Bulat Z, Djukic-Cosic D, Soldatovic D (2010) Antagonism between cadmium and magnesium: a possible role of magnesium in therapy of cadmium intoxication. Magnes Res 23(1):19–26. PubMedCrossRefGoogle Scholar
  25. 25.
    National Research Council (US) (2011) Committee for the Update of the Guide for the Care and Use of Laboratory Animals, 8th edn, Washington (DC), National Academies Press (US)Google Scholar
  26. 26.
    Jacquillet G, Barbier O, Cougnon M, Tauc M, Namorado MC, Martin D, Reyes JL, Poujeol P (2006) Zinc protects renal function during cadmium intoxication in the rat. Am J Physiol Renal Physiol 290(1):F127–F137. CrossRefPubMedGoogle Scholar
  27. 27.
    Ben KL, Hamilton MS, Alexander NJ (1988) Vasectomy-induced autoimmunity: monoclonal antibodies affect sperm function and in vitro fertilization. J Reprod Immunol 13(1):73–84. CrossRefPubMedGoogle Scholar
  28. 28.
    Golshan Iranpour F, Rezazadeh Valojerdi M (2013) The epididymal sperm viability, motility and DNA integrity in dead mice maintained at 4-6oC. Iran J Reprod Med 11(3):195–200PubMedPubMedCentralGoogle Scholar
  29. 29.
    Mdhluli MC, van der Horst G (2002) The effect of oleanolic acid on sperm motion characteristics and fertility of male Wistar rats. Lab Anim 36(4):432–437. CrossRefPubMedGoogle Scholar
  30. 30.
    WHO Organization (2010). Laboratory Manual for the Examination of Human Semen and Sperm-Cervical Mucus Intraction New York: Cambridge University PressGoogle Scholar
  31. 31.
    Esterbauer H, Cheeseman KH (1990) Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol 186:407–421. CrossRefPubMedGoogle Scholar
  32. 32.
    Drury RA, Wallington EA (1980) Carleton’s histological techniques. Oxford University Press, LondonGoogle Scholar
  33. 33.
    Adil M, Kandhare AD, Dalvi G, Ghosh P, Venkata S, Raygude KS, Bodhankar SL (2016) Ameliorative effect of berberine against gentamicin-induced nephrotoxicity in rats via attenuation of oxidative stress, inflammation, apoptosis and mitochondrial dysfunction. Ren Fail 38(6):996–1006. CrossRefPubMedGoogle Scholar
  34. 34.
    Shackelford C, Long G, Wolf J, Okerberg C, Herbert R (2002) Qualitative and quantitative analysis of nonneoplastic lesions in toxicology studies. Toxicol Pathol 30(1):93–96.
  35. 35.
    Waalkes MP, Diwan BA (1999) Cadmium-induced inhibition of the growth and metastasis of human lung carcinoma xenografts: role of apoptosis. Carcinogenesis 20(1):65–70. CrossRefPubMedGoogle Scholar
  36. 36.
    Hikim AP, Amador AG, Klemcke HG, Bartke A, Russell LD (1989) Correlative morphology and endocrinology of Sertoli cells in hamster testes in active and inactive states of spermatogenesis. Endocrinology 125(4):1829–1843.
  37. 37.
    Schlappack OK, Delic JI, Harwood JR, Stanley JA (1988) Protection from radiation-induced damage to spermatogenesis in the androgen pretreated rat. Radiother Oncol 12(3):219–224. CrossRefPubMedGoogle Scholar
  38. 38.
    De Souza Predes F, Diamante MA, Dolder H (2010) Testis response to low doses of cadmium in Wistar rats. Int J Exp Pathol 91:125–131CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Martin LJ, Chen H, Liao X, Allayee H, Shih DM, Lee GS, Hovland DN Jr, Robbins WA, Carnes K, Hess RA, Lusis AJ, Collins MD (2007) FK506, a calcineurin inhibitor, prevents cadmium-induced testicular toxicity in mice. Toxicol Sci 100(2):474–485. CrossRefPubMedGoogle Scholar
  40. 40.
    Koriem KM, Fathi GE, Salem HA, Akram NH, Gamil SA (2013) Protective role of pectin against cadmium-induced testicular toxicity and oxidative stress in rats. Toxicol Mech Methods 23(4):263–272.
  41. 41.
    Ola-Mudathir KF, Suru SM, Fafunso MA, Obioha UE, Faremi TY (2008) Protective roles of onion and garlic extracts on cadmium-induced changes in sperm characteristics and testicular oxidative damage in rats. Food Chem Toxicol 46(12):3604–3611. CrossRefPubMedGoogle Scholar
  42. 42.
    Ozdamar AS, Soylu AG, Culha M, Ozden M, Gokalp A (2004) Testicular oxidative stress. Effects of experimental varicocele in adolescent rats. Urol Int 73(4):343–347. CrossRefPubMedGoogle Scholar
  43. 43.
    Oliveira H, Spano M, Santos C, Pereira Mde L (2009) Adverse effects of cadmium exposure on mouse sperm. Reprod Toxicol 28(4):550–555. CrossRefPubMedGoogle Scholar
  44. 44.
    Bepari M, Maity P, Das M, Choudhury SM (2014) Zinc and αlpha-lipoic acid alleviate cypermethrin induced reproductiv toxicity in mature male Wistar rats. Pharm Sci 4:9–14Google Scholar
  45. 45.
    Sankako MK, Garcia PC, Piffer RC, Dallaqua B, Damasceno DC, Pereira OC (2012) Possible mechanism by which zinc protects the testicular function of rats exposed to cigarette smoke. Pharmacol Rep 64(6):1537–1546. CrossRefPubMedGoogle Scholar
  46. 46.
    Al-Bader A, Omu AE, Dashti H (1999) Chronic cadmium toxicity to sperm of heavy cigarette smokers: immunomodulation by zinc. Arch Androl 43(2):135–140. CrossRefPubMedGoogle Scholar
  47. 47.
    Papadimas J, Bontis J, Ikkos D, Mantalenakis S (1983) Seminal plasma zinc and magnesium in infertile men. Arch Androl 10(3):261–268. CrossRefPubMedGoogle Scholar
  48. 48.
    Sorensen MB, Bergdahl IA, Hjollund NH, Bonde JP, Stoltenberg M, Ernst E (1999) Zinc, magnesium and calcium in human seminal fluid: relations to other semen parameters and fertility. Mol Hum Reprod 5(4):331–337. CrossRefPubMedGoogle Scholar
  49. 49.
    Grosicki A, Małagocki P, Kycko A, Monkiewicz J, Korol W (2015) Magnesium supplements affect selected cadmium toxic actions and uptake of repeated doses of cadmium. Bull Vet Inst Pulawy 59:12–30CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017
Corrected publication December/2017

Authors and Affiliations

  • Nasim Babaknejad
    • 1
    • 2
  • Somaye Bahrami
    • 1
  • Ali Asghar Moshtaghie
    • 1
  • Hashem Nayeri
    • 1
    Email author
  • Parvin Rajabi
    • 3
  • Farhad Golshan Iranpour
    • 4
  1. 1.Department of Biochemistry, Falavarjan BranchIslamic Azad UniversityIsfahanIran
  2. 2.Department of Biology, Faculty of Basic SciencesShahrekord UniversityShahrekordIran
  3. 3.Department of PathologyIsfahan University of Medical SciencesIsfahanIran
  4. 4.Department of Anatomy SciencesIsfahan University of Medical SciensesIsfahanIran

Personalised recommendations