Examining the Early Period Effect of Nilotinib on Hearing: An Experimental Study

Overview

Journal J Int Adv Otol

Publisher Aves

Specialty Otorhinolaryngology

Date 2019 Jul 10

PMID 31287435

Authors

Adem Bora

Kasim Durmus

Hatice Terzi

Emine Elif Altuntas

Affiliations

Soon will be listed here.

Abstract

Objectives: Nilotinib has very few side effects, including neutropenia, thrombocytopenia, cardiotoxicity, high pancreatic lipase, ischemia, and vascular occlusion. We aimed to investigate whether short-term administration of nilotinib had ototoxic effects in rats.

Materials And Methods: Wistar-albino rats were categorized into three groups: group C (administered 0.25 mL of distilled water, no nilotinib), group N-20 (administered 20 mg/kg/day of nilotinib dissolved in distilled water), and group N-50 (administered 50 mg/kg/day of nilotinib dissolved in distilled water). A single dose was administered once per day, at the same hour, over 21 days. Auditory brainstem response (ABR) thresholds were recorded on day 0 and day 21.

Results: There were no changes in ABR threshold values obtained on day 0 (baseline) and on day 21 across all three groups. A statistically significant difference was not found in terms of the mean latency of waves V and III, interpeak latency values of waves III-V, and amplitude ratios of waves III-V and V/Va at baseline and on day 21 across all three groups on within-group or between-group evaluation.

Conclusion: Consequently, further studies are needed that involve different drug doses, prolonged administration of drugs, as well as distortion otoacoustic emission test for the evaluation of cochlear activation and ABR. Furthermore, histopathological studies are needed to indicate whether the cochlea is affected to prove that nilotinib has definitively no ototoxic effect.

References

Cui J, Zhu B, Fang G, Smith E, Brauth S, Tang Y . Effect of the Level of Anesthesia on the Auditory Brainstem Response in the Emei Music Frog (Babina daunchina). PLoS One. 2017; 12(1):e0169449. PMC: 5215878. DOI: 10.1371/journal.pone.0169449. View

Otto D, Hudnell K, Boyes W, Janssen R, Dyer R . Electrophysiological measures of visual and auditory function as indices of neurotoxicity. Toxicology. 1988; 49(2-3):205-18. DOI: 10.1016/0300-483x(88)90001-7. View

Kantarjian H, Hochhaus A, Saglio G, de Souza C, Flinn I, Stenke L . Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd trial. Lancet Oncol. 2011; 12(9):841-51. DOI: 10.1016/S1470-2045(11)70201-7. View

Kim T, Rea D, Schwarz M, Grille P, Nicolini F, Rosti G . Peripheral artery occlusive disease in chronic phase chronic myeloid leukemia patients treated with nilotinib or imatinib. Leukemia. 2013; 27(6):1316-21. DOI: 10.1038/leu.2013.70. View

Sabha N, Au K, Agnihotri S, Singh S, Mangat R, Guha A . Investigation of the in vitro therapeutic efficacy of nilotinib in immortalized human NF2-null vestibular schwannoma cells. PLoS One. 2012; 7(6):e39412. PMC: 3379978. DOI: 10.1371/journal.pone.0039412. View

Damrongwatanasuk R, Fradley M . Cardiovascular Complications of Targeted Therapies for Chronic Myeloid Leukemia. Curr Treat Options Cardiovasc Med. 2017; 19(4):24. DOI: 10.1007/s11936-017-0524-8. View

Schacht J, Hawkins J . Sketches of otohistory. Part 11: Ototoxicity: drug-induced hearing loss. Audiol Neurootol. 2005; 11(1):1-6. DOI: 10.1159/000088850. View

Rea D, Mirault T, Cluzeau T, Gautier J, Guilhot F, Dombret H . Early onset hypercholesterolemia induced by the 2nd-generation tyrosine kinase inhibitor nilotinib in patients with chronic phase-chronic myeloid leukemia. Haematologica. 2014; 99(7):1197-203. PMC: 4077081. DOI: 10.3324/haematol.2014.104075. View

Henley C, Rybak L . Developmental ototoxicity. Otolaryngol Clin North Am. 1993; 26(5):857-71. View

10.

Attili V, Bapsy P, Anupama G, Lokanatha D . Irreversible sensorineural hearing loss due to Imatinib. Leuk Res. 2008; 32(6):991-2. DOI: 10.1016/j.leukres.2007.11.039. View

11.

Lin C, Kao M, Tsai M, Lai C, Wei I, Tsai M . Transient ischemia/hypoxia enhances gentamicin ototoxicity via caspase-dependent cell death pathway. Lab Invest. 2011; 91(7):1092-106. DOI: 10.1038/labinvest.2011.69. View

12.

Shim H, An Y, Kim D, Yoon J, Yoon J . Comparisons of auditory brainstem response and sound level tolerance in tinnitus ears and non-tinnitus ears in unilateral tinnitus patients with normal audiograms. PLoS One. 2017; 12(12):e0189157. PMC: 5734686. DOI: 10.1371/journal.pone.0189157. View

13.

Druker B, Guilhot F, OBrien S, Gathmann I, Kantarjian H, Gattermann N . Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006; 355(23):2408-17. DOI: 10.1056/NEJMoa062867. View

14.

Castagnetti F, Di Raimondo F, De Vivo A, Spitaleri A, Gugliotta G, Fabbiano F . A population-based study of chronic myeloid leukemia patients treated with imatinib in first line. Am J Hematol. 2016; 92(1):82-87. DOI: 10.1002/ajh.24591. View

15.

Lin H, Roberts D, Kay J, Stankovic K . Sensorineural hearing loss following imatinib (Gleevec) administration. Otolaryngol Head Neck Surg. 2011; 146(2):335-7. DOI: 10.1177/0194599811415008. View

16.

Jiang Z, Chen C . Short-term outcome of functional integrity of the auditory brainstem in term infants who suffer perinatal asphyxia. J Neurol Sci. 2017; 376:219-224. DOI: 10.1016/j.jns.2017.03.036. View

17.

Dille M, Ellingson R, McMillan G, Konrad-Martin D . ABR obtained from time-efficient train stimuli for cisplatin ototoxicity monitoring. J Am Acad Audiol. 2013; 24(9):769-81. PMC: 5549621. DOI: 10.3766/jaaa.24.9.2. View

18.

Shi W, Li K, Li Q . [Analysis of risk factors for recurrent sudden sensorineural hearing loss]. Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2018; 32(13):976-978. DOI: 10.13201/j.issn.1001-1781.2018.13.004. View

19.

Smit J, Jahanshahi A, Janssen M, Stokroos R, Temel Y . Hearing assessment during deep brain stimulation of the central nucleus of the inferior colliculus and dentate cerebellar nucleus in rat. PeerJ. 2017; 5:e3892. PMC: 5633028. DOI: 10.7717/peerj.3892. View

20.

Crumling M, King K, Keith Duncan R . Cyclodextrins and Iatrogenic Hearing Loss: New Drugs with Significant Risk. Front Cell Neurosci. 2017; 11:355. PMC: 5676048. DOI: 10.3389/fncel.2017.00355. View