Skip to main content
SpringerLink
Log in

Lithium protects against toxic effects of cadmium in the rat testes

  • Gonadal Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

To investigate the protective effect of Lithium against the toxic effect of Cadmium in the rat testes.

Methods

Twenty four adult male Sprague-Dawley rats were treated with four different regimens: Cadmium only, Cadmium and lithium, lithium only and controls. Rats were sacrificed after 6 weeks and testicular levels of pro-inflammatory cytokine (IL-4), anti-inflammatory cytokine (TNF-α), Pro-apoptotic protein (Bax) and anti-apoptotic protein (Bcl-2) were measured by ELISA while serum levels of FSH, LH, Prolactin and Testosterone were measured using the Vidas parametric system. Antioxidant status (MDA, SOD) was also assessed in serum. Histopathological changes of testes were examined using light and electron microscopy. Immunohistochemical staining for Bax, Bcl-2 and Caspase 3 were performed.

Results

Treatment with lithium was associated with significant reduction in the toxic effects of Cadmium as shown by reduced testicular levels of TNF-α, serum levels of Malondialdehyde and testicular level of Bax, and increased levels of IL-4, Zn-Cu SOD, Bcl-2 and Testosterone. Testicular histopathology showed that Cadmium produced an extensive germ cells apoptosis and the addition of lithium in Cadmium-treated rats significantly reduced cadmium-induced testicular damage.

Conclusion(s)

Lithium has a protective effect against cadmium-induced testicular apoptosis in the rat.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Benoff S, Jacob A, Hurley IR. Male infertility and environmental exposure to lead and cadmium. Hum Reprod Update. 2000;6:107–21.

    Article  CAS  PubMed  Google Scholar 

  2. Laskey JW, Rehnberg GL, Laws SC, Hein JF. Reproductive effects of low acute doses of cadmium chloride in adult male rats. Toxicol Appl Pharmacol. 1984;73:250–5.

    Article  CAS  PubMed  Google Scholar 

  3. Laskey JW, Rehnberg GL, Laws SC, Hein JF. Age-related dose response of selected reproductive parameters to acute cadmium chloride exposure in the male Lon-Evans rat. J Toxicol Environ Health. 1986;19:393–401.

    Article  CAS  PubMed  Google Scholar 

  4. Gennart JP, Buchet JP, Roels H, Ghyselen P, Ceulemans E, Lauwerys R. Fertility of male workers exposed to cadmium, lead or manganese. Am J Epidemiol. 1992;135:1208–19.

    CAS  PubMed  Google Scholar 

  5. Foote RH. Cadmium affects testes and semen of rabbits exposed before and after puberty. Reprod Toxicol. 1999;13:269–77.

    Article  CAS  PubMed  Google Scholar 

  6. Benoff S, Hurley IR, Mandel FS, Paine T, Jacob A, Cooper GW, et al. Use of mannose ligands in IVF screens to mimic zona pellucida-induced acrosome reactions and predict fertilization success. Mol Hum Reprod. 1997;3(10):839–46.

    Article  CAS  PubMed  Google Scholar 

  7. Xu LC, Wang SY, Yang XF, Wang XR. Effects of cadmium on rat sperm motility evaluated with computer assisted sperm analysis. Biomed Environ Sci. 2001 Dec;14(4):312–7.

    CAS  PubMed  Google Scholar 

  8. Perry DK, Smyth MJ, Stennicke HR, Salvesen GS, Duriez P, Poirier GG, et al. Zinc is a potent inhibitor of the apoptotic protease, Caspase-3. A novel target for zinc in the inhibition of apoptosis. Cell Death Differ. 1997;4:29–33.

    Article  CAS  PubMed  Google Scholar 

  9. Xu G, Zhou G, Jin T, Jin T, Zhou T, Hammarstrom S, et al. Apoptosis and p53 gene expression in male reproductive tissues of cadmium exposed rats. Biometals. 1999;12:131–9.

    Article  CAS  PubMed  Google Scholar 

  10. Zhou T, Zhou G, Song W, Eguchi N, Lu W, Lundin E, et al. Cadmium-induced apoptosis and changes in expression of p53, c-jun and MT-I genes in testes and ventral prostate of rats. Toxicology. 1999;142:1–13.

    Article  CAS  PubMed  Google Scholar 

  11. Chen RW, Chuang DM. Long term lithium treatment suppresses p53 and Bax expression but increases Bcl-2 expression. A prominent role in neuroprotection against excitotoxicity. J Biol Chem. 1999;274:6039–42.

    Article  CAS  PubMed  Google Scholar 

  12. Hiroi T, Wei H, Hough C. Leeds, Chaung DM. Protracted lithium treatment protects against the ER stress elicited by thepsigargin in rat PC12 cells: role of intracellular calcium, GRP78 and Bcl-2. Pharmacogenomics J. 2005;5:102–11.

    Article  CAS  PubMed  Google Scholar 

  13. Omu AE, Al-Qattan F, Abdul-hadi FM, Fatinikun MT, Fernandes S. Seminal immune response in infertile men with leukocytospermia: effect on antioxidant activity. Eur J Obstet Gynecol Reprod Biol. 1999;86:195–202.

    Article  CAS  PubMed  Google Scholar 

  14. Kehinde EO, Mojiminiyi OA, Mahmoud AH, Al-Awadi KA, Al-Hunayan A, Omu AE. The significance of measuring the time course of serum malondialdehyde concentration in patients with torsion of the testis. J Urol. 2003;169:2177–80.

    Article  CAS  PubMed  Google Scholar 

  15. Johnsen SG. Testicular biopsy score-count-a method for registration of spermatogenesis in human testes: normal values and result of 335 hypogonadal males. Hormones. 1970;1:2–25.

    Article  CAS  PubMed  Google Scholar 

  16. Eguchi Y, Srinivasan A, Tomaselli KJ, Shimizu S, Tsujimoto Y. ATP-dependent steps in Apoptotic Signal Transduction. Cancer Research. 1999;59:2174–81.

    CAS  PubMed  Google Scholar 

  17. Ikediobi CO, Badisa VL, Ayuk-Takem LT, Latinwo LM, West J. Response of antioxidant enzymes and redox metabolites to cadmium-induced oxidative stress in CRL-1439 normal rat liver cells. Int J Mol Med. 2004;14:87–92.

    CAS  PubMed  Google Scholar 

  18. El-Demerdash FM, Yousef MI, Kedwany FS, Baghdadi HH. 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. 2004;2:1563–71.

    Google Scholar 

  19. Yadav N, Khandelwal S. Effect of Picroliv on cadmium induced testicular damage in rat. Food Chem Toxicol. 2008;46:494–501.

    Article  CAS  PubMed  Google Scholar 

  20. Siu ER, Mruk DD, Porto CS, Cheng CY. Cadmium-induced testicular injury. Toxicol Appl Pharmacol. 2009;238:240–9.

    Article  CAS  PubMed  Google Scholar 

  21. Chuang DM. The antiapoptotic actions of mood stabilizers: molecular mechanisms and therapeutic potentials. Ann NY Acad Sci. 2005;1053:195–204.

    Article  CAS  PubMed  Google Scholar 

  22. Rowe MK, Chuang DM. Lithium neuroprotection: molecular mechanisms and clinical implications. Expert Rev Mol Med. 2004;6:1–18.

    Article  PubMed  Google Scholar 

  23. Sahebgharani M, Neijati M, Sepehrizadeh Z. Lithium chloride protects PC12 pheochromocytoma cell line from morphine-induced apoptosis. Arch Iran Med. 2008;11:639–48.

    CAS  PubMed  Google Scholar 

  24. Xu J, Culman J, Blume A, Brecht S, Gohlke P. Chronic treatment with a low dose lithium protects the brain against ischemic injury by reducing apoptotic death. Stroke. 2003;34:1287–92.

    Article  CAS  PubMed  Google Scholar 

  25. Song L, Zhou T. Jope RS Lithium facilitates apoptotic signaling induced by activation of the Fas death domain-containing receptor. BMC Neurosci. 2004;5:20.

    Article  PubMed  Google Scholar 

  26. Ghosh D, Biswas NM, Ghosh PK. Effect of lithium chloride on adrenocortical activity in male rats: evidence of dose and duration dependent response. Indian J Physiol Pharmacol. 1990;34:263–6.

    CAS  PubMed  Google Scholar 

  27. Thakur SC, Thakur SS, Chaube SK, Singh SP. Subchronic supplementation of lithium carbonate induces reproductive system toxicity in male rat. Reproductive Toxicol. 2003;17:683–90.

    Article  CAS  Google Scholar 

  28. Hockenbery DM, Oltvai ZN, Yin X-M, Milliman CL, Korsmeyer SJ. Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell. 1993;75:241–51.

    Article  CAS  PubMed  Google Scholar 

  29. Lenox RH, Hahn CG. Overview of the mechanism of action of lithium in the brain: fifty-year update. J Clin Psychiatry. 2000;61 Suppl 9:5–15.

    CAS  PubMed  Google Scholar 

  30. Bielecka AM, Obuchowicz E. Antiapoptotic action of lithium and valproate. Pharmacol Rep. 2008;60:771–82.

    CAS  PubMed  Google Scholar 

Download references

Disclosure information

All authors have nothing to declare.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat, 13110, Kuwait

    Majedah Al-Azemi & Alexander E. Omu

  2. College of Nursing, Public Authority for Applied Education and Training (PAAET), Safat, Kuwait

    Florence E. Omu

  3. Department of Surgery, Faculty of Medicine, Kuwait University, Safat, Kuwait

    Elijah O. Kehinde

  4. Department of Pathology, Faculty of Medicine, Kuwait University, Safat, Kuwait

    Jeroham T. Anim

  5. Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Safat, Kuwait

    Mabayoje A. Oriowo

Authors
  1. Majedah Al-Azemi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Florence E. Omu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elijah O. Kehinde
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jeroham T. Anim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mabayoje A. Oriowo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alexander E. Omu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Majedah Al-Azemi.

Additional information

Capsule

Lithium protection against toxic effect of Cadmium in rat testes suggests its potential preventive uses in male infertility among smokers.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Al-Azemi, M., Omu, F.E., Kehinde, E.O. et al. Lithium protects against toxic effects of cadmium in the rat testes. J Assist Reprod Genet 27, 469–476 (2010). https://doi.org/10.1007/s10815-010-9426-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-010-9426-3

Keywords

Search

Navigation