Protective Effects of Melatonin and Alpha Lipoic Acid Against Cisplatin-Induced Ototoxicity

Mehmet Akif DÜNDAR , BAHAR KELEŞ, Yavuz Uyar , Mehmet Öz

  • Mehmet Akif DÜNDAR: Necmettin Erbakan Üniversitesi Tıp Fakültesi
  • BAHAR KELEŞ: SELÇUK ÜNİVERSİTESİ
  • Yavuz Uyar: Prof.Dr. Cemil Taşçıoğlu Şehir Hastanesi
  • Mehmet Öz: Aksaray Üniversitesi
  • Year : 2025
  • Vol : 41
  • Issue : 1
  •  Page : 36-41
ABSTRACT
Aim: To investigate the potential protective effects of melatonin and alpha-lipoic acid against cisplatin-induced ototoxicity in a rat model using brainstem auditory evoked potentials.
Materials and Methods: Sixty Sprague-Dawley rats were randomly divided into six groups: control, cisplatin-only, melatonin-only, alpha-lipoic acid-only, cisplatin+melatonin, and cisplatin+alpha-lipoic acid. Cisplatin was administered as a single intraperitoneal injection (10 mg/kg). Melatonin (4 mg/kg) and alpha-lipoic acid (100 mg/kg) were administered daily for eight days, starting one day before cisplatin. Brainstem Auditory Evoked Potentials were measured at baseline and on days 3, 7, and 15. Wave latencies, interpeak latencies, hearing thresholds, and waveform morphology were analyzed.
Results: Cisplatin administration resulted in significant prolongation of wave V latency and increased hearing thresholds. Melatonin treatment significantly mitigated cisplatin-induced changes in wave V latency and hearing thresholds compared to cisplatin alone (p<0.05). Alpha-lipoic acid did not demonstrate significant protection against cisplatin-induced changes. Both melatonin and alpha-lipoic acid groups showed alterations in wave latencies when administered alone. Waveform distortions were most prevalent in the cisplatin group, with lower incidence in melatonin and alpha-lipoic acid treatment groups.
Conclusions: Treatment with melatonin significantly mitigates cisplatin-induced ototoxicity in rats, likely due to its potent antioxidant properties. This finding supports the potential of melatonin as a therapeutic strategy to prevent or minimize hearing loss in patients receiving cisplatin chemotherapy. However, alpha-lipoic acid did not exhibit significant protection in this study, warranting further investigation.
Keywords: Cisplatin, ototoxicity, melatonin, alpha-lipoic acid, antioxidants
Cite this Article As : Dundar MA, Colpan B, Uyar Y, Oz M. Protective Effects of Melatonin and Alpha Lipoic Acid Against Cisplatin-Induced Ototoxicity. Selcuk Med J 2025;41(1): 36-41

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Conflict of interest : The authors declare that they have no conflict of interest.
This article is published under the CC BY-NC 4.0 license.
Selcuk Medical Journal
2025, Vol. 41 (1)
ISSN: 1017-6616
E-ISSN: 2149-8059
Received : , Accepted : , Published Online :

References

  1. 1. Ravi R, Somani SM, Rybak L. Mechanism of Cisplatin Ototoxicity: Antioxidant System. Pharmacol Toxicol. 1995 Jun;76(6):386-94. doi: 10.1111/j.1600-0773.1995.tb00167.x.
  2. 2. Tuncer S, Dalkılıç N, Dundar MA, et al. Comparative Effects of Alpha Lipoic Acid and Melatonin on Cisplatin-Induced Neurotoxicity. Int J Neurosci. 2010 Oct;120(10):655-63. https://doi.org/10.3109/00207454.2010.510916.
  3. 3. Reiter RJ, Tan DX, Galano A. Melatonin: Exceeding Expectations. Physiology (Bethesda). 2014 Sep;29(5):325-33. doi: 10.1152/physiol.00011.2014.
  4. 4. Carrillo‐Vico A, Guerrero JM, Lardone PJ, et al. A Review of the Multiple Actions of Melatonin on the Immune System. Endocrine. 2005 Jul;27(2):189-200. doi: 10.1385/ENDO:27:2:189.
  5. 5. Shay KP, Moreau RF, Smith EJ, et al. Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential. Biochim Biophys Acta. 2009 Oct;1790(10):1149-60. doi: 10.1016/j.bbagen.2009.07.026.
  6. 6. Altıntoprak N, Aydın S, Şanlı A, et al. The Protective Effect of Intratympanic Alpha Lipoic Acid on Cisplatin-Induced Ototoxicity on Rats. J Int Adv Otol. 2014; 10: 217-221 DOI: 10.5152/iao.2014.369
  7. 7. Picton TW, Hillyard SA, Krausz HI, et al. Human auditory evoked potentials. I. Evaluation of components. Electroencephalogr Clin Neurophysiol. 1974 Feb;36(2):179-90. doi: 10.1016/0013-4694(74)90155-2.
  8. 8. Chiappa KH. Evoked potentials in clinical medicine. 3rd ed. Philadelphia: Lippincott-Raven, 1997: 145-7
  9. 9. Krishnan A. Auditory Brainstem Evoked Responses: Clinical and Research Applications. 1st Edition. San Diego, CA : Plural Publishing, Inc., 2023: 31-46
  10. 10. Hatzopoulos S, Stefano M, Campbell K, et al. (2001). Cisplatin Ototoxicity in the Sprague Dawley Rat Evaluated by Distortion Product Otoacoustic Emissions. Audiology. 2001 May;40:253 - 264. https://doi.org/10.3109/00206090109073119.
  11. 11. Hatzopoulos S, Di Stefano M, Albertin A, et al. Evaluation of cisplatin ototoxicity in a rat animal model. Ann N Y Acad Sci. 1999 Nov 28;884:211-25. doi: 10.1111/j.1749-6632.1999.tb08643.x.
  12. 12. Kim KH, Lee B, Kim YR, et al. Evaluating protective and therapeutic effects of alpha-lipoic acid on cisplatin-induced ototoxicity. Cell Death Dis. 2018 Aug 1;9(8):827. doi: 10.1038/s41419-018-0888-z.
  13. 13. Ramkumar V, Mukherjea D, Dhukhwa A, et al. Oxidative Stress and Inflammation Caused by Cisplatin Ototoxicity. Antioxidants (Basel). 2021 Nov 29;10(12):1919. doi: 10.3390/antiox10121919.
  14. 14. Manta O, Sarafidis M, Vasileiou N, et al. Development and Evaluation of Automated Tools for Auditory-Brainstem and Middle-Auditory Evoked Potentials Waves Detection and Annotation. Brain Sci. 2022 Dec 6;12(12):1675. doi: 10.3390/brainsci12121675.
  15. 15. Dammeyer P, Hellberg V, Wallin I, et al. Cisplatin and oxaliplatin are toxic to cochlear outer hair cells and both target thioredoxin reductase in organ of Corti cultures. Acta Otolaryngol. 2014 May;134(5):448-54. doi: 10.3109/00016489.2013.879740.
  16. 16. Nikitkina YY, Kryukov AI, Kunel’skaya NL, et al. Hearing loss when taking cisplatin, depending on the dose. Russian otorhinolaryngology. 2023 January;22(5):53-59 DOI:10.18692/1810-4800-2023-5-53-59
  17. 17. Samizadeh MA, Fallah H, Toomarisahzabi M, et al. Parkinson’s Disease: A Narrative Review on Potential Molecular Mechanisms of Sleep Disturbances, REM Behavior Disorder, and Melatonin. Brain Sci. 2023 Jun 6;13(6):914. doi: 10.3390/brainsci13060914.
  18. 18. Zduńska A, Cegielska J, Domitrz I. The Pathogenetic Role of Melatonin in Migraine and Its Theoretic Implications for Pharmacotherapy: A Brief Overview of the Research. Nutrients. 2022 Aug 15;14(16):3335. doi: 10.3390/nu14163335.
  19. 19. Serra LSM, Araujo JG, Vieira ALS, et al. Role of melatonin in prevention of age-related hearing loss. PLoS One. 2020 Feb 10;15(2):e0228943. doi: 10.1371/journal.pone.0228943. eCollection 2020.
  20. 20. Reíter RJ, Tan DX, Korkmaz A, et al. Drug-mediated ototoxicity and tinnitus: alleviation with melatonin. J Physiol Pharmacol. 2011 Apr;62(2):151-7.
  21. 21. Lateef Al-Awsi GR, Arshed U, Arif A, et al. The Chemoprotective Potentials of Alpha-lipoic Acid against Cisplatin-induced Ototoxicity: A Systematic Review. Curr Med Chem. 2024;31(23):3588-3603. doi: 10.2174/0929867330666230509162513.
  22. 22. De Freitas MR, De Silva VC, Brito GAC, et al. Distortion-product otoacoustic emissions and auditory brainstem responses sensitivity assessment in cisplatin-induced ototoxicity in rats. Braz J Otorhinolaryngol. 2009 Jul-Aug;75(4):476-84. doi: 10.1016/S1808-8694(15)30483-3.