European Archives of Oto-Rhino-Laryngology

, Volume 270, Issue 8, pp 2231–2237 | Cite as

Protective effect of thymoquinone against cisplatin-induced ototoxicity

  • Mustafa Sagit
  • Ferhat Korkmaz
  • Alper Akcadag
  • Mehmet Akıf Somdas


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.


Cisplatin Thymoquinone Ototoxicity Distortion product otoacoustic emission Auditory brain stem responses 


Conflict of interest

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


  1. 1.
    Rybak LP, Mukherjea D, Jajoo S, Ramkumar V (2009) Cisplatin ototoxicity and protection: clinical and experimental studies. Tohoku J Exp Med 219:177–186PubMedCrossRefGoogle Scholar
  2. 2.
    Williams CJ, Whitehouse JM (1979) Cis-platinum: a new anticancer agent. Br Med J 1:1689–1691PubMedCrossRefGoogle Scholar
  3. 3.
    Hartmann JT, Lipp HP (2003) Toxicity of platinum compounds. Expert Opin Pharmacother 4:889–901PubMedCrossRefGoogle Scholar
  4. 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 76:404–408PubMedCrossRefGoogle Scholar
  5. 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 269:2185–2188PubMedCrossRefGoogle Scholar
  6. 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 28:73–80PubMedCrossRefGoogle Scholar
  7. 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 137:747–752PubMedCrossRefGoogle Scholar
  8. 8.
    Kalkanis JG, Whitworth C, Rybak LP (2004) Vitamin E reduces cisplatin ototoxicity. Laryngoscope 114:538–542PubMedCrossRefGoogle Scholar
  9. 9.
    Campbell KC, Meech RP, Rybak LP, Hughes LF (1999) d-Methionine protects against cisplatin damage to the stria vascularis. Hear Res 138:13–28PubMedCrossRefGoogle Scholar
  10. 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 111:1147–1155PubMedCrossRefGoogle Scholar
  11. 11.
    Huang X, Whitworth CA, Rybak LP (2007) Ginkgo biloba extract (EGb 761) protects against cisplatin-induced ototoxicity in rats. Otol Neurotol 28:828–833PubMedCrossRefGoogle Scholar
  12. 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 201:81–89PubMedCrossRefGoogle Scholar
  13. 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 5:227–237PubMedCrossRefGoogle Scholar
  14. 14.
    Hyppolito MA, de Oliveira JA, Rossato M (2006) Cisplatin ototoxicity and otoprotection with sodium salicylate. Eur Arch Otorhinolaryngol 263:798–803PubMedCrossRefGoogle Scholar
  15. 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 32:228–234PubMedCrossRefGoogle Scholar
  16. 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 269:45–52PubMedCrossRefGoogle Scholar
  17. 17.
    Gökçe A, Oktar S, Koc A, Yonden Z (2011) Protective effects of thymoquinone against methotrexate-induced testicular injury. Hum Exp Toxicol 30:897–903PubMedCrossRefGoogle Scholar
  18. 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–E171Google Scholar
  19. 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 33:637–643PubMedCrossRefGoogle Scholar
  20. 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 75:1356–1361PubMedCrossRefGoogle Scholar
  21. 21.
    Nagi MN, Mansour MA (2000) Protective effect of thymoquinone against doxorubicin-induced cardiotoxicity in rats: a possible mechanism of protection. Pharmacol Res 41:283–289PubMedCrossRefGoogle Scholar
  22. 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 47:153–159PubMedGoogle Scholar
  23. 23.
    Halliwell B (1994) Free radicals, antioxidants, and human disease: curiosity, cause, or consequence? Lancet 344:721–724PubMedCrossRefGoogle Scholar
  24. 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 20:143–151PubMedCrossRefGoogle Scholar
  25. 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 26:87–98PubMedCrossRefGoogle Scholar
  26. 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 62:938–946PubMedCrossRefGoogle Scholar
  27. 27.
    Woo CC, Kumar AP, Sethi G, Tan KH (2012) Thymoquinone: potential cure for inflammatory disorders and cancer. Biochem Pharmacol 83:443–451PubMedCrossRefGoogle Scholar
  28. 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 69:5575–5583PubMedCrossRefGoogle Scholar
  29. 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 67:7782–7788PubMedCrossRefGoogle Scholar
  30. 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 12:330–342PubMedCrossRefGoogle Scholar
  31. 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 29:87PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Mustafa Sagit
    • 1
    • 3
  • Ferhat Korkmaz
    • 1
  • Alper Akcadag
    • 2
  • Mehmet Akıf Somdas
    • 1
  1. 1.Department of ENTKayseri Training and Research HospitalKayseriTurkey
  2. 2.Subdepartment of AudiologyKayseri Training and Research HospitalKayseriTurkey
  3. 3.Kayseri Eğitim ve Araştırma Hastanesi KBB Kliniği, Sanayi Mah.KayseriTurkey

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