Skip to main content
SpringerLink
Log in

The effect of resveratrol on the prevention of cisplatin ototoxicity

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

Abstract

One of the most important adverse effects of cisplatin, a chemotherapeutic agent which is widely used in the treatment of cancer patients, is hearing loss. This has primarily been associated with the loss of inner ear hairy and spiral ganglion cells due to oxidative stress. Resveratrol is known to be an antioxidant agent, which has the theoretical potential of preventing cisplatin-related ototoxicity. This experimental study was approved by Animal Ethics Committee of Inonu University (2008–20) and supported by Inonu University Scientific Research Projects Support Fund (2009–17). Thirty-four 3-month-old Wistar albino female rats weighing 210–270 g were used in the study. The animals were allocated into four groups: in cisplatin group (Group A), a single dose of 12 mg/kg cisplatin was administered intraperitoneally to 10 rats; in cisplatin + resveratrol group (Group B), a single dose of 12 mg/kg cisplatin and 10 mg/kg resveratrol were administered intraperitoneally for 5 days to 10 rats; in resveratrol group (Group C), 10 mg/kg resveratrol was administered intraperitoneally for 5 days to seven rats and in control group (Group D), resveratrol solvent (5% alcohol–95% physiological saline) was administered intraperitoneally for 5 days to seven rats. Resveratrol administration has begun 1 day before cisplatin administration in the group treated with cisplatin and resveratrol combination. Distortion product otoacoustic emission (DPOAE) (Grason Stadler, Madison, USA) measurements were performed in the same ear of all rats (right ear) under general anesthesia at baseline, 1st and 5th days after drug administration. Statistically significant distortion product amplitude reductions were found in the cisplatin group at 1,418, 2,003, 3,363, 5,660, 8,003 and 9,515 Hz frequencies. Whereas in the cisplatin + resveratrol group, statistically significant difference was found between 1st and 5th day measurements only at 3,996 Hz frequency. No significant differences were noted between the measurements either in the resveratrol or in the control groups. According to these results, cisplatin-related ototoxicity has been greatly prevented by resveratrol use.

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

Similar content being viewed by others

References

  1. McKeage MJ (1995) Comparative adverse effects of platinum drugs. Drug Safety 13:228–244

    Article  PubMed  CAS  Google Scholar 

  2. Li Y, Womer RB, Silber JH (2004) Predicting cisplatin ototoxicity in children: the influence of age and the cumulative dose. Eur J Cancer 40:2445–2451

    Article  PubMed  CAS  Google Scholar 

  3. Knight KRG, Kraemer DF, Neuwelt EA (2005) Ototoxicity in children receiving platinum chemotherapy: underestimating a commonly occurring toxicity that may influence academic and social development. J Clin Oncol 23:8588–8896

    Article  PubMed  Google Scholar 

  4. Chen WC, Jackson A, Budnick AS, Pfister DG, Kraus DH, Hunt MA, Stambuk H, Levegrun S, Wolden SL (2006) Sensorineural hearing loss in combined modality treatment of nasopharyngeal carcinoma. Cancer 106:820–829

    Article  PubMed  Google Scholar 

  5. 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 

  6. Reiter RJ, Tan DX, Korkmaz A, Fuentes-Broto L (2011) Drug-mediated ototoxicity and tinnitus: alleviation with melatonin. J Physiol Pharmacol 62:151–157

    PubMed  CAS  Google Scholar 

  7. Giordano P, Lorito G, Ciorba A, Martini A, Hatzopoulos S (2006) Protection against cisplatin ototoxicity in a Sprague–Dawley rat animal model. Acta Otorhinolaryngol Ital 26:198–207

    PubMed  CAS  Google Scholar 

  8. Campbell KC, Meech RP, Klemens JJ, Gerberi MT, Dyrstad SS, Larsen DL, Mitchell DL, El-Azizi M, Verhulst SJ, Hughes LF (2007) Prevention of noise- and drug-induced hearing loss with d-methionine. Hear Res 226:92–103

    Article  PubMed  CAS  Google Scholar 

  9. 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 

  10. Breuil AC, Jeandet P, Adrian M, Chopin F, Pirio N, Meunier P, Bessis R (1999) Characterization of a pterostilbene dehydrodimer produced by laccase of Botrytis cinerea. Phytopathology 89:298–302

    Article  PubMed  CAS  Google Scholar 

  11. Savouret JF, Quesne M (2002) Resveratrol and cancer: a review. Biomed Pharmacother 56:84–87

    Article  PubMed  CAS  Google Scholar 

  12. Ravi R, Somani SM, Rybak LP (1995) Mechanism of cisplatin ototoxicity: antioxidant defense system. Pharmacol Toxicol 76:386–394

    Article  PubMed  CAS  Google Scholar 

  13. Tsukasaki N, Whitworth CA, Rybak LP (2000) Acute changes in cochlear potentials due to cisplatin. Hear Res 149:189–198

    Article  PubMed  CAS  Google Scholar 

  14. Klis SF, O’Leary SJ, Hamers FP, De Groot JC, Smoorenburg GF (2000) Reversible cisplatin ototoxicity in the albino guinea pig. Neuroreport 11:623–626

    Article  PubMed  CAS  Google Scholar 

  15. Van Ruijven MWM, de Groot JCMJ, Klis SFL, Smoorenburg G (2005) Cochlear targets of cisplatin: an electrophysiological and morphological time-sequence study. Hear Res 205:241–248

    Article  PubMed  Google Scholar 

  16. Alam SA, Ikeda K, Oshima T, Suzuki M, Kawase T, Kikuchi T, Takasaka T (2000) Cisplatin-induced apoptotic cell death in Mongolian gerbil cochlea. Hear Res 141:28–38

    Article  PubMed  CAS  Google Scholar 

  17. Clerici WJ, DiMartino DL, Prasad MR (1995) Direct effect of reactive oxygen species on cochlear outer hair cells. Hear Res 84:30–40

    Article  PubMed  CAS  Google Scholar 

  18. Clerici WJ, Hensley K, DiMartino DL, Butterfield DA (1996) Direct detection of ototoxicant-induced reactive oxygen species generation in cochlear explants. Hear Res 98:116–124

    Article  PubMed  CAS  Google Scholar 

  19. Kopke RD, Liu W, Gabaizadeh R, Jacono A, Feghali J, Spray D, Garcia P, Steinman H, Malgrange B, Ruben RJ, Rybak L, Van de Water T (1997) The use of organotypic cultures of Corti’s organ to study the protective effects of antioxidant molecules on cisplatin induced damage of auditory hair cells. Am J Otol 18:559–571

    PubMed  CAS  Google Scholar 

  20. Dehne N, Lautermann J, Petrat F, Rauen U, de Groot H (2001) Cisplatin ototoxicity: involvement of iron and enhanced formation of superoxide anion radicals. Toxicol Appl Pharmacol 174:27–34

    Article  PubMed  CAS  Google Scholar 

  21. Bonabi S, Caelers A, Monge A, Huber A, Bodmer D (2008) Resveratrol protects auditory hair cells from gentamicin toxicity. Ear Nose Throat J 87:570–573

    PubMed  Google Scholar 

  22. Seidman M, Babu S, Tang W, Naem E, Quirk WS (2003) Effects of resveratrol on acoustic trauma. Otolaryngol Head Neck Surg 129:463–470

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was funded by Inonu University Scientific Research Project Units (2009–17). This experiment was performed in proper with the guidelines of animal research which is setted by the National Institute of Health.

Author information

Authors and Affiliations

  1. Department of Otolaryngology Head and Neck Surgery, Faculty of Medicine, İnonu University, Malatya, Turkey

    T. Erdem, Tuba Bayindir & E. Selimoglu

  2. Department of Otolaryngology, Zekai Tahir Obstetrics and Gynecology Hospital, Ankara, Turkey

    A. Filiz

  3. Department of Pharmacology, Faculty of Medicine, Bezmi Alem University, Istanbul, Turkey

    M. Iraz

Authors
  1. T. Erdem
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tuba Bayindir
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Filiz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Iraz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E. Selimoglu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tuba Bayindir.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Erdem, T., Bayindir, T., Filiz, A. et al. The effect of resveratrol on the prevention of cisplatin ototoxicity. Eur Arch Otorhinolaryngol 269, 2185–2188 (2012). https://doi.org/10.1007/s00405-011-1883-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00405-011-1883-5

Keywords

Search

Navigation