Skip to main content
Log in

Protective effect of thymoquinone against cisplatin-induced ototoxicity

  • Otology
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

The aim of this study was to investigate the potential protective effect of thymoquinone against cisplatin-induced ototoxicity. This study is a prospective, controlled experimental animal study. Experiments were performed on 30 healthy female Sprague-Dawley rats. Thirty animals were divided into three groups of 10 animals each. Group 1 received an intraperitoneal (i.p.) injection of cisplatin 15 mg/kg. Group 2 received i.p. thymoquinone 40 mg/kg/day for 2 days prior to cisplatin injection and third day i.p. cisplatin 15 mg/kg was administered concomitantly. Group 2 continued to receive i.p. thymoquinone until fifth day. Group 3 received i.p. thymoquinone 40 mg/kg/day for 5 days. Pretreatment distortion product otoacoustic emissions (DPOAE) and auditory brain stem responses (ABR) testing from both ears were obtained from the animals in all groups. After the baseline measurements, drugs were injected intraperitonally. After an observation period of 3 days, DPOAE measurements and ABR testing were obtained again and compared with the pretreatment values. There was no statistically significant difference between pre and post-treatment DPOAE responses and ABR thresholds group 2 and 3. However, group 1 demonstrated significant deterioration of the ABR thresholds and DPOAE responses. Our results suggest that DPOAE responses and ABR thresholds were preserved in the cisplatin plus TQ-treated group when compared with the group receiving cisplatin alone. According to these results, cisplatin-induced ototoxicity may be prevented by thymoquinone use in rats.

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

Similar content being viewed by others

References

  1. Rybak LP, Mukherjea D, Jajoo S, Ramkumar V (2009) Cisplatin ototoxicity and protection: clinical and experimental studies. Tohoku J Exp Med 219:177–186

    Article  PubMed  CAS  Google Scholar 

  2. Williams CJ, Whitehouse JM (1979) Cis-platinum: a new anticancer agent. Br Med J 1:1689–1691

    Article  PubMed  CAS  Google Scholar 

  3. Hartmann JT, Lipp HP (2003) Toxicity of platinum compounds. Expert Opin Pharmacother 4:889–901

    Article  PubMed  CAS  Google Scholar 

  4. Yumusakhuylu AC, Yazici M, Sari M, Binnetoglu A, Kosemihal E, Akdas F, Sirvanci S, Yuksel M, Uneri C, Tutkun A (2012) Protective role of resveratrol against cisplatin induced ototoxicity in guinea pigs. Int J Pediatr Otorhinolaryngol 76:404–408

    Article  PubMed  Google Scholar 

  5. Erdem T, Bayindir T, Filiz A, Iraz M, Selimoglu E (2011) The effect of resveratrol on the prevention of cisplatin ototoxicity. Eur Arch Otorhinolaryngol 269:2185–2188

    Article  PubMed  Google Scholar 

  6. Lopez-Gonzalez MA, Guerrero JM, Rojas F, Delgado F (2000) Ototoxicity caused by cisplatin is ameliorated by melatonin and other antioxidants. J Pineal Res 28:73–80

    Article  PubMed  CAS  Google Scholar 

  7. Daldal A, Odabasi O, Serbetcioglu B (2007) The protective effect of intratympanic dexamethasone on cisplatin-induced ototoxicity in guinea pigs. Otolaryngol Head Neck Surg 137:747–752

    Article  PubMed  Google Scholar 

  8. Kalkanis JG, Whitworth C, Rybak LP (2004) Vitamin E reduces cisplatin ototoxicity. Laryngoscope 114:538–542

    Article  PubMed  CAS  Google Scholar 

  9. Campbell KC, Meech RP, Rybak LP, Hughes LF (1999) d-Methionine protects against cisplatin damage to the stria vascularis. Hear Res 138:13–28

    Article  PubMed  CAS  Google Scholar 

  10. Feghali JG, Liu W, Van De Water TR (2001) L-n-acetyl-cysteine protection against cisplatin-induced auditory neuronal and hair cell toxicity. Laryngoscope 111:1147–1155

    Article  PubMed  CAS  Google Scholar 

  11. Huang X, Whitworth CA, Rybak LP (2007) Ginkgo biloba extract (EGb 761) protects against cisplatin-induced ototoxicity in rats. Otol Neurotol 28:828–833

    Article  PubMed  Google Scholar 

  12. Lynch ED, Gu R, Pierce C, Kil J (2005) Reduction of acute cisplatin ototoxicity and nephrotoxicity in rats by oral administration of allopurinol and ebselen. Hear Res 201:81–89

    Article  PubMed  CAS  Google Scholar 

  13. Church MW, Blakley BW, Burgio DL, Gupta AK (2004) WR-2721 (Amifostine) ameliorates cisplatin-induced hearing loss but causes neurotoxicity in hamsters: dose-dependent effects. J Assoc Res Otolaryngol 5:227–237

    Article  PubMed  Google Scholar 

  14. Hyppolito MA, de Oliveira JA, Rossato M (2006) Cisplatin ototoxicity and otoprotection with sodium salicylate. Eur Arch Otorhinolaryngol 263:798–803

    Article  PubMed  Google Scholar 

  15. Xu O, Liu Y, Li X, Yang Y, Zhang Z, Wang N, Zhang Y, Lu H (2011) Protective effects of Salvia miltiorrhiza against cisplatin-induced ototoxicity in guinea pigs. Am J Otolaryngol 32:228–234

    Article  PubMed  CAS  Google Scholar 

  16. Yazici ZM, Meric A, Midi A, Arınc YV, Kahya V, Hafız G (2012) Reduction of cisplatin ototoxicity in rats by oral administration of pomegranate extract. Eur Arch Otorhinolaryngol 269:45–52

    Article  PubMed  Google Scholar 

  17. Gökçe A, Oktar S, Koc A, Yonden Z (2011) Protective effects of thymoquinone against methotrexate-induced testicular injury. Hum Exp Toxicol 30:897–903

    Article  PubMed  Google Scholar 

  18. Basarslan F, Yilmaz N, Ates S, Ozgur T, Tutanc M, Motor VK, Arica V, Yilmaz C, Inci M, Buyukbas S (2012) Protective effects of thymoquinone on vancomycin-induced nephrotoxicity in rats. Hum Exp Toxicol 16:E167–E171

    Google Scholar 

  19. Nader MA, el-Agamy DS, Suddek GM (2010) Protective effects of propolis and thymoquinone on development of atherosclerosis in cholesterol-fed rabbits. Arch Pharm Res 33:637–643

    Article  PubMed  CAS  Google Scholar 

  20. Badary OA, Nagi MN, Al-Shabanah OA, Al-Sawaf HA, Al-Sohaibani MO, Al-Bekairi AM (1997) Thymoquinone ameliorates the nephrotoxicity induced by cisplatin in rodents and potentiates its antitumor activity. Can J Physiol Pharmacol 75:1356–1361

    Article  PubMed  CAS  Google Scholar 

  21. Nagi MN, Mansour MA (2000) Protective effect of thymoquinone against doxorubicin-induced cardiotoxicity in rats: a possible mechanism of protection. Pharmacol Res 41:283–289

    Article  PubMed  CAS  Google Scholar 

  22. Nagi MN, Alam K, Badary OA, Al-Shabanah OA, Al-Sawaf HA, Al-Bekairi AM (1999) Thymoquinone protects against carbon tetrachloride hepatotoxicity in mice via an antioxidant mechanism. Biochem Mol Biol Int 47:153–159

    PubMed  CAS  Google Scholar 

  23. Halliwell B (1994) Free radicals, antioxidants, and human disease: curiosity, cause, or consequence? Lancet 344:721–724

    Article  PubMed  CAS  Google Scholar 

  24. Mansour MA, Nagi MN, El-Khatib AS, Al-Bekairi AM (2002) Effects of thymoquinone on antioxidant enzyme activities, lipid peroxidation and DT-diaphorase in different tissues of mice: a possible mechanism of action. Cell Biochem Funct 20:143–151

    Article  PubMed  CAS  Google Scholar 

  25. Badary OA, Taha RA, Gamal el-Din AM, Abdel-Wahab MH et al (2003) Thymoquinone is a potent superoxide anion scavenger. Drug Chem Toxicol 26:87–98

    Article  PubMed  CAS  Google Scholar 

  26. Banerjee S, Padhye S, Azmi A, Wang Z, Philip PA, Kucuk O, Sarkar FH, Mohammad RM (2010) Review on molecular and therapeutic potential of thymoquinone in cancer. Nutr Cancer 62:938–946

    Article  PubMed  CAS  Google Scholar 

  27. Woo CC, Kumar AP, Sethi G, Tan KH (2012) Thymoquinone: potential cure for inflammatory disorders and cancer. Biochem Pharmacol 83:443–451

    Article  PubMed  CAS  Google Scholar 

  28. Banerjee S, Kaseb AO, Wang Z, Kong D, Mohammad M, Padhye S, Sarkar FH, Mohammad RM (2009) Antitumor activity of gemcitabine and oxaliplatin is augmented by thymoquinone in pancreatic cancer. Cancer Res 69:5575–5583

    Article  PubMed  CAS  Google Scholar 

  29. Kaseb AO, Chinnakannu K, Chen D, Sivanandam A, Tejwani S, Menon M, Dou QP, Reddy GP (2007) Androgen receptor and E2F–1 targeted thymoquinone therapy for hormone-refractory prostate cancer. Cancer Res 67:7782–7788

    Article  PubMed  CAS  Google Scholar 

  30. Gali-Muhtasib H, Ocker M, Kuester D, Krueger S, El-Hajj Z, Diestel A, Evert M, El-Najjar N, Peters B, Jurjus A, Roessner A, Schneider-Stock R (2008) Thymoquinone reduces mouse colon tumor cell invasion and inhibits tumor growth in murine colon cancer models. J Cell Mol Med 12:330–342

    Article  PubMed  Google Scholar 

  31. Jafri SH, Glass J, Shi R, Zhang S, Prince M, Kleiner-Hancock H (2010) Thymoquinone and cisplatin as a therapeutic combination in lung cancer: in vitro and in vivo. J Exp Clin Cancer Res 29:87

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

None of the authors have a financial relationship with any organization that sponsored the research.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mustafa Sagit.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sagit, M., Korkmaz, F., Akcadag, A. et al. Protective effect of thymoquinone against cisplatin-induced ototoxicity. Eur Arch Otorhinolaryngol 270, 2231–2237 (2013). https://doi.org/10.1007/s00405-012-2254-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00405-012-2254-6

Keywords

Navigation