Skip to main content

Advertisement

Log in

Protective effects of orally administered thymol against titanium dioxide nanoparticle–induced testicular damage

  • Research Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

In this study, we investigated the potential of thymol and its mode of action to protect against the titanium dioxide (TiO2) nanoparticle–induced testicular damage. Twenty-four rats were randomly divided into four groups: control group, TiO2 (100 mg/kg BW/day) group, TiO2 + thymol (10 mg/kg BW/day) group, and TiO2 + thymol (30 mg/kg BW/day) group. With the exception of the control group, all animals received orally TiO2 nanoparticles for 60 days. In treatment groups, animals were given orally thymol 1 h before TiO2 nanoparticles. Epididymal sperm parameters, testicular histopathology, and spermatogenesis assessments were performed for evaluation of the TiO2 and thymol effects on the testis. Furthermore, antioxidative enzyme activities such as catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), and malondialdehyde (MDA), glutathione (GSH) levels and ferric-reducing antioxidant power (FRAP) value were measured. Intragastric administration of TiO2 for 60 consecutive days caused a significant decrease in sperm quality, widespread histopathological alteration, and significantly induced oxidative stress as manifested by elevated MDA levels and a remarkable decline in antioxidant enzyme activities such as CAT, SOD, and GPx, and also FRAP and GSH levels in testis tissue. Nearly all of these alterations were significantly ameliorated in the groups that orally received thymol before TiO2 nanoparticles administration. The results of this study demonstrated that thymol improved the spermatogenesis defects induced by TiO2 nanoparticles in rats in a dose-dependent manner by protecting the testes against the testicular toxicity. Reduction in TiO2 nanoparticle–induced oxidative stress may have a major role in this protective effect.

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

Similar content being viewed by others

References

  • Abd-Elhakim YM, Mohamed WA (2016) Assessment of the role of thymol in combating chromium (VI)-induced oxidative stress in isolated rat erythrocytes in vitro. Toxicol Environ Chem 98:1227–1240

    Article  CAS  Google Scholar 

  • Aboelwafa HR, Yousef HN (2015) The ameliorative effect of thymol against hydrocortisone-induced hepatic oxidative stress injury in adult male rats. Biochem Cell Biol 93:282–289

    Article  CAS  Google Scholar 

  • Agarwal A, Makker K, Sharma R (2008) Clinical relevance of oxidative stress in male factor infertility: an update. Am J Reprod Immunol 59:2–11

    Article  CAS  Google Scholar 

  • Alaee S, Ilani M (2017) Effect of titanium dioxide nanoparticles on male and female reproductive systems. J Adv Med Sci Appl Technol 3:3–8

    Article  Google Scholar 

  • Asghari MH, Moloudizargari M, Baeeri M, Baghaei A, Rahimifard M, Solgi R, Jafari A, Aminjan HH, Hassani S, Moghadamnia AA (2017) On the mechanisms of melatonin in protection of aluminum phosphide cardiotoxicity. Arch Toxicol 91:3109–3120

    Article  CAS  Google Scholar 

  • Benzie IF, Strain JJ (1996) The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem 239:70–76

    Article  CAS  Google Scholar 

  • Cardoso ES, Santana TA, Diniz PBF, Montalvão MM, Bani CC, Thomazzi SM (2016) Thymol accelerates the recovery of the skeletal muscle of mice injured with cardiotoxin. J Pharm Pharmacol 68:352–360

    Article  CAS  Google Scholar 

  • Chen E, Ruvalcaba M, Araujo L, Chapman R, Chin W-C (2008) Ultrafine titanium dioxide nanoparticles induce cell death in human bronchial epithelial cells. J Exp Nanosci 3:171–183

    Article  CAS  Google Scholar 

  • El-Sayed ESM, Mansour AM, Abdul-Hameed MS (2016) Thymol and carvacrol prevent doxorubicin-induced cardiotoxicity by abrogation of oxidative stress, inflammation, and apoptosis in rats. J Biochem Mol Toxicol 30:37–44

    Article  CAS  Google Scholar 

  • Ghaffarian-Bahraman A, Shahroozian I, Jafari A, Ghazi-Khansari M (2014) Protective effect of magnesium and selenium on cadmium toxicity in the isolated perfused rat liver system. Acta Med Iran 52:872–878

    Google Scholar 

  • Ghasemnejad-berenji M, Ghazi-Khansari M, Yazdani I, Saravi SSS, Nobakht M, Abdollahi A, Ansari JM, Ghasemnejad-berenji H, Pashapour S, Dehpour AR (2017) Rapamycin protects testes against germ cell apoptosis and oxidative stress induced by testicular ischemia-reperfusion. Iran J Basic Med Sci 20:905

    Google Scholar 

  • Ghasemnejad-berenji M, Ghazi-Khansari M, Pashapour S, Jafari A, Yazdani I, Ghasemnejad-berenji H, Saravi SSS, Sadeghpour S, Nobakht M, Abdollahi A (2018a) Synergistic effect of rapamycin and metformin against germ cell apoptosis and oxidative stress after testicular torsion/detorsion-induced ischemia/reperfusion in rats. Biomed Pharmacother 105:645–651

    Article  CAS  Google Scholar 

  • Ghasemnejad-Berenji M, Ghazi-Khansari M, Yazdani I, Nobakht M, Abdollahi A, Ghasemnejad-Berenji H, Mohajer Ansari J, Pashapour S, Dehpour A (2018b) Effect of metformin on germ cell-specific apoptosis, oxidative stress and epididymal sperm quality after testicular torsion/detorsion in rats. Andrologia 50:e12846

    Article  Google Scholar 

  • Hong F, Si W, Zhao X, Wang L, Zhou Y, Chen M, Ge Y, Zhang Q, Wang Y, Zhang J (2015a) TiO2 nanoparticle exposure decreases spermatogenesis via biochemical dysfunctions in the testis of male mice. J Agric Food Chem 63:7084–7092

    Article  CAS  Google Scholar 

  • Hong F, Zhao X, Si W, Ze Y, Wang L, Zhou Y, Hong J, Yu X, Sheng L, Liu D (2015b) Decreased spermatogenesis led to alterations of testis-specific gene expression in male mice following nano-TiO2 exposure. J Hazard Mater 300:718–728

    Article  CAS  Google Scholar 

  • Iavicoli I, Leso V, Fontana L, Bergamaschi A (2011) Toxicological effects of titanium dioxide nanoparticles: a review of in vitro mammalian studies. Eur Rev Med Pharmacol Sci 15:481–508

    CAS  Google Scholar 

  • Jafari A, Rasmi Y, Hajaghazadeh M, Karimipour M (2018) Hepatoprotective effect of thymol against subchronic toxicity of titanium dioxide nanoparticles: biochemical and histological evidences. Environ Toxicol Pharmacol 58:29–36

    Article  CAS  Google Scholar 

  • Karimipour M, Javanmard MZ, Ahmadi A, Jafari A (2018) Oral administration of titanium dioxide nanoparticle through ovarian tissue alterations impairs mice embryonic development. Int J Reprod Biomed 16:397

    CAS  Google Scholar 

  • Meeran N, Fizur M, Javed H, Al Taee H, Azimullah S, Ojha SK (2017) Pharmacological properties and molecular mechanisms of thymol: prospects for its therapeutic potential and pharmaceutical development. Front Pharmacol 8:380

    Article  Google Scholar 

  • Narayana K, D’Souza UJ, Rao KS (2002) Ribavirin-induced sperm shape abnormalities in Wistar rat. Mutat Res/Genet Toxicol Enviro Mutagen 513:193–196

    Article  CAS  Google Scholar 

  • Orazizadeh M, Khorsandi L, Absalan F, Hashemitabar M, Daneshi E (2014) Effect of beta-carotene on titanium oxide nanoparticles-induced testicular toxicity in mice. J Assist Reprod Genet 31:561–568

    Article  Google Scholar 

  • Palabiyik S, Karakus E, Halici Z, Cadirci E, Bayir Y, Ayaz G, Cinar I (2016) The protective effects of carvacrol and thymol against paracetamol–induced toxicity on human hepatocellular carcinoma cell lines (HepG2). Hum Exp Toxicol 35:1252–1263

    Article  CAS  Google Scholar 

  • Park E-J, Yi J, Chung K-H, Ryu D-Y, Choi J, Park K (2008) Oxidative stress and apoptosis induced by titanium dioxide nanoparticles in cultured BEAS-2B cells. Toxicol Lett 180:222–229

    Article  CAS  Google Scholar 

  • Shakeel M, Jabeen F, Shabbir S, Asghar MS, Khan MS, Chaudhry AS (2016) Toxicity of nano-titanium dioxide (TiO 2-NP) through various routes of exposure: a review. Biol Trace Elem Res 172:1–36

    Article  CAS  Google Scholar 

  • Weir A, Westerhoff P, Fabricius L, Hristovski K, Von Goetz N (2012) Titanium dioxide nanoparticles in food and personal care products. Environ Sci Technol 46:2242–2250

    Article  CAS  Google Scholar 

  • Yazdani I, Majdan R, Ghasemnejad-berenji M, Dehpour AR (2019) Comparison of multiple doses of cyclosporine a on germ cell apoptosis and epididymal sperm parameters after testicular ischemia/reperfusion in rats. Exp Mol Pathol 104271

Download references

Funding

This research has been supported by Urmia University of Medical Sciences and health services (1395-01-34-2453).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Morteza Ghasemnejad-Berenji.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Responsible editor: Philippe Garrigues

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

Jafari, A., Karimipour, M., Khaksar, M.R. et al. Protective effects of orally administered thymol against titanium dioxide nanoparticle–induced testicular damage. Environ Sci Pollut Res 27, 2353–2360 (2020). https://doi.org/10.1007/s11356-019-06937-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-019-06937-7

Keywords

Navigation