Skip to main content
SpringerLink
Log in

Protective effects of green and chemical zinc oxide nanoparticles on testis histology, sperm parameters, oxidative stress markers and androgen production in rats treated with cisplatin

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Cancer treatment with cisplatin (CP) is associated with adverse side effects on male reproductive tissues. Although beneficial effects of zinc oxide nanoparticles (ZnO NPs) in cancer therapy have received considerable attention, data related to the protective effects of green ZnO NPs against CP-induced male reproductive dysfunctions are limited. Forty-five rats were divided into 9 groups including G1 (control), G2 (sham), G3 (ZnO bulk), G4 (green ZnO NPs), G5 (chemical ZnO NPs), G6 (CP), G7 (CP + ZnO bulk), G8 (CP + green ZnO NPs), and G9 (CP + chemical ZnO NPs). CP was administrated (5 mg/kg/week) for 4 weeks, and animals were simultaneously treated with different forms of ZnO (5 mg/kg/day). Testis histology, sperm parameters, oxidative stress markers, testosterone concentration, and expression of genes related in steroidogenesis were analyzed in different experimental groups. Testis tissue damage and epididymal sperm disorders induced by CP attenuated when animals were treated with different forms of ZnO, especially green ZnO NPs. Decreased testosterone concentration and increased MDA level in CP-treated rats were reversed following administration different forms of ZnO, especially green and chemical ZnO NPs. Co-administration of ZnO NPs to CP-treated rats restored the suppressive effects of CP on activities of antioxidant enzymes (SOD, GPX, CAT) and the transcription of the STAR gene. None of the ZnO forms had a significant regulatory effect on the expression of CYP11A1 in CP-treated rats. The results showed that in most of the evaluated factors, green ZnO NPs showed a greater protective effect than other forms of ZnO.

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
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

CP:

Cisplatin (cis-diamminedichloroplatinum)

ZnO:

Zinc oxide

NPs:

Nanoparticles

SOD:

Superoxide dismutase

GPX:

Glutathione peroxidase

CAT:

Catalase

MDA:

Malondialdehyde

STAR:

Steroidogenic acute regulatory protein

CYP11A1:

Cytochrome P450 family 11 subfamily A member 1

ROS:

Reactive oxygen species

FDA:

Food and Drug Administration

TEM:

Transmission electron microscopy

PSA:

Particle size analyzer

TBARS:

Thiobarbituric acid reactive substance

References

  • Agarwal H, Kumar SV, Rajeshkumar S et al (2017) A review on green synthesis of zinc oxide nanoparticles–an eco-friendly approach. Resour Effic Techno 3:406–413

    Google Scholar 

  • Aitken RJ, Curry BJ (2011) Redox regulation of human sperm function: From the physiological control of sperm capacitation to the etiology of infertility and DNA damage in the germ line. Antioxid Redox Signal 14:367–381

    Article  CAS  Google Scholar 

  • Alazouny ZM, Mohamed EM, Ahmed GA et al (2014) Effect of cyclosporine A on the structure of adult albino rat testis and the role of lycopene supplementation: A histological and immunohistochemical study. Egyptian J Histol 37:292–303

    Article  Google Scholar 

  • Al-Bader M, Kilarkaje N (2015) Effects of bleomycin, etoposide and cisplatin treatment on Leydig cell structure and transcription of steroidogenic enzymes in rat testis. Eur J pharmacol 747:150–159

    Article  CAS  Google Scholar 

  • Anan HH, Zidan RA (2018) EL-Baset SAA & Ali MM, Ameliorative effect of zinc oxide nanoparticles on cyclophosphamide induced testicular injury in adult rat. Tissue Cell 54:80–93

    Article  CAS  Google Scholar 

  • Bandeira M, Giovanela M, Roesch-Ely M, Devine DM, Da Silva CJ et al (2020) Green synthesis of zinc oxide nanoparticles: A review of the synthesis methodology and mechanism of formation. Sustain Chem Pharm 15:100223. https://doi.org/10.1016/j.scp.2020.100223

    Article  Google Scholar 

  • Bara N, Kaul G (2018) Enhanced steroidogenic and altered antioxidant response by ZnO nanoparticles in mouse testis Leydig cells. Toxicol Ind Health 34:571–588

    Article  CAS  Google Scholar 

  • Beytur A, Ciftci O, Oguz F, Oguzturk H, Yılmaz F et al (2012) Montelukast attenuates side effects of cisplatin including testicular, spermatological, and hormonal damage in male rats. Cancer Chemother Pharmacol 69:207–213

    Article  CAS  Google Scholar 

  • Bisht G, Rayamajhi S (2016) ZnO nanoparticles: a promising anticancer agent. Nanobiomedicine 3:3-9. https://hrcak.srce.hr/157716

  • Chu Q, Chi ZH, Zhang X, Liang D, Wang X, Zhao Y, Zhang L, Zhang P et al (2016) A potential role for zinc transporter 7 in testosterone synthesis in mouse Leydig tumor cells. Int J Mol Med 37:1619–1626

    Article  CAS  Google Scholar 

  • El-Beltagi EM, Elwan WM, El-Bakry NAM, Salah EF et al (2017) Histological and immunohistochemical study on the effect of gibberellic acid on the seminiferous tubules of testis of adult albino rat and the possible protective role of grape seeds proanthocyanidin extract. Tanta Med J 45:79–91

    Article  Google Scholar 

  • El-Maddawy ZK, El Naby WSHA (2019) Protective effects of zinc oxide nanoparticles against doxorubicin induced testicular toxicity and DNA damage in male rats. Toxicol Res 8:654–662

    Article  CAS  Google Scholar 

  • Elshama SS, Abdallah ME, Abdel-Karim RI (2018) Zinc oxide nanoparticles: therapeutic benefits and toxicological hazards. Open Nanomed J 5:16–22. https://doi.org/10.2174/1875933501805010016

    Article  Google Scholar 

  • Favareto APA, Fernandez CDB, Da Silva DAF, Anselmo-Franci JA, Kempinas WDG et al (2011) Persistent impairment of testicular histology and sperm motility in adult rats treated with cisplatin at peri-puberty. Basic Clin Pharmacol Toxicol 109:85–96

    Article  CAS  Google Scholar 

  • Fouad AA, Qutub HO, Fouad AEA, Audeh AM, Al-Melhim WN et al (2017) Epigallocatechin-3-gallate counters cisplatin toxicity of rat testes. Pharm Biol 55:1710–1714

    Article  CAS  Google Scholar 

  • Gao H, Yallampalli U, Yallampalli C et al (2012) Gestational protein restriction reduces expression of Hsd17b2 in rat placental labyrinth. Biol Reprod 87:1–7

    Article  Google Scholar 

  • Garcia MMS, Acquier A, Suarez G, Gomez NV, Gorostizaga A, Mendez CF, Paz C et al (2012) Cisplatin inhibits testosterone synthesis by a mechanism that includes the action of reactive oxygen species (ROS) at the level of CYP11A1. Chem Biol Interact 199:185–191

    Article  Google Scholar 

  • Hamman JH (2008) Composition and applications of aloe vera leaf gel. Molecules 13:1599–1616

    Article  CAS  Google Scholar 

  • Ilbey YO, Ozbek E, Cekmen M, Simsek A, Otunctemur A, Somay A et al (2009) Protective effect of curcumin in cisplatin-induced oxidative injury in rat testis: Mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways. Hum Reprod 24:1717–1725

    Article  CAS  Google Scholar 

  • Ilbey YO, Ozbek E, Simsek A, Otunctemur A, Cekmen M, Somay A et al (2009) Potential chemoprotective effect of melatonin in cyclophosphamide-and cisplatin-induced testicular damage in rats. Fertil Steril 92:1124–1132

    Article  CAS  Google Scholar 

  • Kaya K, Ciftci O, Cetin A, Dogan H, Basak N et al (2015) Hesperidin protects testicular and spermatological damages induced by cisplatin in rats. Andrologia 47:793–800

    Article  CAS  Google Scholar 

  • Kei S (1978) Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method. Clin Chim Acta 90:37–43

    Article  Google Scholar 

  • Meligy FY, Abo Elgheed AT, Alghareeb SM et al (2019) Therapeutic effect of adipose-derived mesenchymal stem cells on cisplatin induced testicular damage in adult male albino rat. Ultrastruct Pathol 43:28–55

  • Mitra S, Subia B, Patra P, Chandra S, Debnath N, Das S, Banerjee R, Kundu SC, Pramanik P, Goswami A et al (2012) Porous ZnO nanorod for targeted delivery of doxorubicin: In vitro and in vivo response for therapeutic applications. J Mater Chem 22:24145–24154

    Article  CAS  Google Scholar 

  • Mohamed DA, Abdelrahman SA (2019) The possible protective role of zinc oxide nanoparticles (ZnONPs) on testicular and epididymal structure and sperm parameters in nicotine-treated adult rats (a histological and biochemical study). Cell tissue Res 375:543–558

    Article  CAS  Google Scholar 

  • Mohammadnejad D, Abedelahi A (2012) Degenerative effect of cisplatin on testicular germinal epithelium. Adv Pharm Bull 2:173–177

    PubMed  PubMed Central  Google Scholar 

  • Narayana K, Al-Bader M, Mousa A, Khan KM et al (2012) Molecular effects of chemotherapeutic drugs and their modulation by antioxidants in the testis. European J pharmacol 674:207–216

    Article  CAS  Google Scholar 

  • Patra JK, Das G, Fraceto LF, Campos EVR, del Pilar Rodriguez-Torres M, Acosta-Torres LS, Diaz-Torres LA, Grillo R, Swamy MK, Sharma S, Habtemariam S (2018) Nano based drug delivery systems: recent developments and future prospects. J nanobiotechnology 16:71. https://doi.org/10.1186/s12951-018-0392-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prasad AS, Bao B (2019) Molecular mechanisms of zinc as a pro-antioxidant mediator: clinical therapeutic implications. Antioxidants 8:164. https://doi.org/10.3390/antiox8060164

    Article  CAS  PubMed Central  Google Scholar 

  • Razavi R, Molaei R, Moradi M, Tajik H, Ezati P, Yordshahi AS et al (2020) Biosynthesis of metallic nanoparticles using mulberry fruit (Morus alba L.) extract for the preparation of antimicrobial nanocellulose film. Appl Nanosci 10:465–476

    Article  CAS  Google Scholar 

  • Rizk SM, Zaki HF, Mina MA et al (2014) Propolis attenuates doxorubicin-induced testicular toxicity in rats. Food Chem Toxicol 67:176–186

    Article  CAS  Google Scholar 

  • Santhoshkumar J, Kumar SV, Rajeshkumar S et al (2017) Synthesis of zinc oxide nanoparticles using plant leaf extract against urinary tract infection pathogen. Resour Effic Techno 3:459–465

    Google Scholar 

  • Santhoshkumar J, Rajeshkumar S, Kumar SV et al (2017) Phyto-assisted synthesis, characterization and applications of gold nanoparticles–a review. Biochem Biophys Rep 11:46–57

    CAS  PubMed  PubMed Central  Google Scholar 

  • Silici S, Ekmekcioglu O, Eraslan G, Demirtas A et al (2009) Antioxidative effect of royal jelly in cisplatin-induced testes damage. Urol 74:545–551

    Article  Google Scholar 

  • Soni KK, Kim HK, Choi BR, Karna KK, You JH, Cha JS, Shin YS, Lee SW, Kim CY, Park JK et al (2016) Dose-dependent effects of cisplatin on the severity of testicular injury in Sprague Dawley rats: Reactive oxygen species and endoplasmic reticulum stress. Drug Des Devel Ther 10:3959–3968

    Article  CAS  Google Scholar 

  • Swain PS, Rao SB, Rajendran D, Dominic G, Selvaraju S et al (2016) Nano zinc, an alternative to conventional zinc as animal feed supplement: A review. Anim Nutr 2:134–141

    Article  Google Scholar 

  • Torabi F, Shafaroudi MM, Rezaei N et al (2017) Combined protective effect of zinc oxide nanoparticles and melatonin on cyclophosphamide-induced toxicity in testicular histology and sperm parameters in adult Wistar rats. Int J Reprod Biomed 15:403–412

    CAS  PubMed  PubMed Central  Google Scholar 

  • Turk G, Atessahin A, Sonmez M, Ceribasi AO, Yuce A (2008) Improvement of cisplatin-induced injuries to sperm quality, the oxidant-antioxidant system, and the histologic structure of the rat testis by ellagic acid. Fertil Steril 89:1474–1481

    Article  CAS  Google Scholar 

  • Vandebriel RJ, De Jong WH (2012) A review of mammalian toxicity of ZnO nanoparticles. Nanotechnol Sci Appl 5:61–71

    Article  CAS  Google Scholar 

Download references

Funding

This work was funded by a grant from the Research Council of the Shahid Chamran University of Ahvaz (Grant No. 98/3/05/14909).

Author information

Authors and Affiliations

  1. Department of Basic Sciences, Faculty of Veterinary Medicine, Division of Histology , Shahid Chamran University of Ahvaz, Ahvaz, Iran

    Naeem Erfani Majd & Akram Hajirahimi

  2. Stem Cells and Transgenic Technology Research Center, Shahid Chamran University of Ahvaz, Ahvaz, Iran

    Naeem Erfani Majd & Mohammad Reza Tabandeh

  3. Department of Basic Sciences, Division of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

    Mohammad Reza Tabandeh

  4. Department of Food Hygiene and Quality Control, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

    Rahim Molaei

Authors
  1. Naeem Erfani Majd
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akram Hajirahimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohammad Reza Tabandeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rahim Molaei
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

N.E.M. was a supervisor and collaborated in histological studies. M.R.T. was a supervisor and collaborated in the molecular, biochemical, and statistical analyses. R.M. was an advisor and collaborated in nanoparticle preparation and chemical characterization. A.H. was a Ph.D. student and collaborated in performing a thesis and writing an article. All authors revised the article critically for important intellectual content and approved the final study.

Corresponding author

Correspondence to Naeem Erfani Majd.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All experimental protocols were approved by the ethics committee for research in animals and humans of the Shahid Chamran University of Ahvaz, Ahvaz, Iran (EE/99.3.02.11770/scu.ac.ir). This article does not contain any studies with human participants performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Erfani Majd, N., Hajirahimi, A., Tabandeh, M.R. et al. Protective effects of green and chemical zinc oxide nanoparticles on testis histology, sperm parameters, oxidative stress markers and androgen production in rats treated with cisplatin. Cell Tissue Res 384, 561–575 (2021). https://doi.org/10.1007/s00441-020-03350-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-020-03350-2

Keywords

Search

Navigation