CC BY-NC-ND 4.0 · Int Arch Otorhinolaryngol 2019; 23(03): e267-e275
DOI: 10.1055/s-0038-1676654
Original Research
Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil

The Effects of Riluzole on Cisplatin-induced Ototoxicity

1   Department of Otorhinolaryngology, Kanuni Sultan Süleyman Education and Research Hospital, İstanbul, Turkey
,
Kadir Kemal Uygur
2   Department of Otorhinolaryngology, Gazi University Faculty of Medicine, Ankara, Turkey
,
Çağıl Gökdoğan
3   Department of Otorhinolaryngology, Muğla Sıtkı Koçman University Faculty of Medicine, Muğla, Turkey
,
Çiğdem Elmas
4   Department of Histology and Embryology, Gazi University Faculty of Medicine, Ankara, Turkey
,
Güleser Göktaş
5   Department of Histology and Embryology, Lokman Hekim University, Faculty of Medicine, Ankara, Turkey
› Institutsangaben
Weitere Informationen

Publikationsverlauf

04. Juli 2018

21. Oktober 2018

Publikationsdatum:
01. März 2019 (online)

Abstract

Introduction Riluzole (2-amino-6-trifluoromethoxy benzothiazole) is known as a neuroprotective, antioxidant, antiapoptotic agent. It may have beneficial effects on neuronal cell death due to cisplatin-induced ototoxicity.

Objective To evaluate the effect of riluzole on cisplatin-induced ototoxicity in guinea pigs.

Methods Twenty-four guinea pigs, studied in three groups, underwent auditory brainstem response evaluation using click and 8 kHz tone burst stimuli. Subsequently, 5 mg/kg of cisplatin were administered to all animals for 3 days intraperitoneally (i.p.) to induce ototoxicity. Half an hour prior to cisplatin, groups 1, 2 and 3 received 2 ml of saline i.p., 6 mg/kg of riluzole hydrochloride i.p., and 8 mg/kg of riluzole hydrochloride i.p., respectively, for 3 days. The auditory brainstem responses were repeated 24 hours after the last drug administration. The cochleae were analyzed by transmission electron microscopy (TEM).

Results After drug administiration, for 8,000 Hz stimulus, group 1 had significantly higher threshold shifts when compared with groups 2 (p < 0.05) and 3 (p < 0.05), and there was no significant difference in threshold shifts between groups 2 and 3 (p > 0.05). Transmission electron microscopy findings demonstrated the protective effect of riluzole on the hair cells and the stria vascularis, especially in the group treated with 8 mg/kg of riluzole hydrochloride.

Conclusion We can say that riluzole may have a protective effect on cisplatin- induced ototoxicity. However, additional studies are needed to confirm these results and the mechanisms of action of riluzole.

Note

This study was done in Gazi University Faculty of Medicine, Ankara, Turkey.


This study was approved and monitored by Gazi University Animal Experiments Local Ethics Committee (G. Ü. ET - B.30.2.GÜN.0.05.06.00/80-6489.


Financial Disclosure

The study was supported by a grant from the Scientific Research Projects Commission.


 
  • References

  • 1 Rybak LP, Ramkumar V. Ototoxicity. Kidney Int 2007; 72 (08) 931-935
  • 2 Bokemeyer C, Berger CC, Hartmann JT. , et al. Analysis of risk factors for cisplatin-induced ototoxicity in patients with testicular cancer. Br J Cancer 1998; 77 (08) 1355-1362
  • 3 Rybak LP, Mukherjea D, Jajoo S, Ramkumar V. Cisplatin ototoxicity and protection: clinical and experimental studies. Tohoku J Exp Med 2009; 219 (03) 177-186
  • 4 Casares C, Ramírez-Camacho R, Trinidad A, Roldán A, Jorge E, García-Berrocal JR. Reactive oxygen species in apoptosis induced by cisplatin: review of physiopathological mechanisms in animal models. Eur Arch Otorhinolaryngol 2012; 269 (12) 2455-2459
  • 5 Rybak LP. Mechanisms of cisplatin ototoxicity and progress in otoprotection. Curr Opin Otolaryngol Head Neck Surg 2007; 15 (05) 364-369
  • 6 van Ruijven MW, de Groot JCMJ, Klis SFL, Smoorenburg GF. The cochlear targets of cisplatin: an electrophysiological and morphological time-sequence study. Hear Res 2005; 205 (1-2): 241-248
  • 7 van Ruijven MW, de Groot JCMJ, Smoorenburg GF. Time sequence of degeneration pattern in the guinea pig cochlea during cisplatin administration. A quantitative histological study. Hear Res 2004; 197 (1-2): 44-54
  • 8 Cardinaal RM, de Groot JCMJ, Huizing EH, Veldman JE, Smoorenburg GF. Dose-dependent effect of 8-day cisplatin administration upon the morphology of the albino guinea pig cochlea. Hear Res 2000; 144 (1-2): 135-146
  • 9 Feghali JG, Liu W, Van De Water TR. L-n-acetyl-cysteine protection against cisplatin-induced auditory neuronal and hair cell toxicity. Laryngoscope 2001; 111 (07) 1147-1155
  • 10 Ramírez-Camacho R, García-Berrocal JR, Buján J, Martín-Marero A, Trinidad A. Supporting cells as a target of cisplatin-induced inner ear damage: therapeutic implications. Laryngoscope 2004; 114 (03) 533-537
  • 11 Cheah BC, Vucic S, Krishnan AV, Kiernan MC. Riluzole, neuroprotection and amyotrophic lateral sclerosis. Curr Med Chem 2010; 17 (18) 1942-199
  • 12 Bellingham MC. A review of the neural mechanisms of action and clinical efficiency of riluzole in treating amyotrophic lateral sclerosis: what have we learned in the last decade?. CNS Neurosci Ther 2011; 17 (01) 4-31
  • 13 Ettaiche M, Fillacier K, Widmann C, Heurteaux C, Lazdunski M. Riluzole improves functional recovery after ischemia in the rat retina. Invest Ophthalmol Vis Sci 1999; 40 (03) 729-736
  • 14 Lang-Lazdunski L, Heurteaux C, Mignon A. , et al. Ischemic spinal cord injury induced by aortic cross-clamping: prevention by riluzole. Eur J Cardiothorac Surg 2000; 18 (02) 174-181
  • 15 Wang J, Dib M, Lenoir M. , et al. Riluzole rescues cochlear sensory cells from acoustic trauma in the guinea-pig. Neuroscience 2002; 111 (03) 635-648
  • 16 Ruel J, Wang J, Pujol R, Hameg A, Dib M, Puel JL. Neuroprotective effect of riluzole in acute noise-induced hearing loss. Neuroreport 2005; 16 (10) 1087-1090
  • 17 Roth JA, Sridhar S, Singleton ST. Effect of glutamate and riluzole on manganese-induced apoptotic cell signaling in neuronally differentiated mouse P19 Cells. Neurochem Int 2012; 61 (01) 25-33
  • 18 Koh JY, Kim DK, Hwang JY, Kim YH, Seo JH. Antioxidative and proapoptotic effects of riluzole on cultured cortical neurons. J Neurochem 1999; 72 (02) 716-723
  • 19 Mu X, Azbill RD, Springer JE. Riluzole improves measures of oxidative stress following traumatic spinal cord injury. Brain Res 2000; 870 (1-2): 66-72
  • 20 Liu AYC, Mathur R, Mei N, Langhammer CG, Babiarz B, Firestein BL. Neuroprotective drug riluzole amplifies the heat shock factor 1 (HSF1)- and glutamate transporter 1 (GLT1)-dependent cytoprotective mechanisms for neuronal survival. J Biol Chem 2011; 286 (04) 2785-2794
  • 21 Yang J, Bridges K, Chen KY, Liu AYC. Riluzole increases the amount of latent HSF1 for an amplified heat shock response and cytoprotection. PLoS One 2008; 3 (08) e2864
  • 22 Chang G, Guo Y, Jia Y. , et al. Protective effect of combination of sulforaphane and riluzole on glutamate-mediated excitotoxicity. Biol Pharm Bull 2010; 33 (09) 1477-1483
  • 23 Elmas Ç, Bahçelioğlu M, Erdoğan D. , et al. Immunohistochemical and Ultrastructural Changes Related To Methylphenidate In Rat Pituitary and Pineal Glands. J Neurol Sci 2012; 29 (03) 476-493
  • 24 Elmas Ç, Erdoğan D, Göktaş G. , et al. İyonize Radyasyon Uygulaması Yapılmış Rat Pineal Bezi Üzerinde Melatoninin Koruyucu Etkisi Var mıdır? Kronobiyolojik ve Elektron Mikroskobik Çalışma. Kafkas Univ Vet Fak Derg 2013; 19 (01) 153-160
  • 25 Ocho S, Iwasaki S, Umemura K, Hoshino T. A new model for investigating hair cell degeneration in the guinea pig following damage of the stria vascularis using a photochemical reaction. Eur Arch Otorhinolaryngol 2000; 257 (04) 182-187
  • 26 Thomas JP, Lautermann J, Liedert B, Seiler F, Thomale J. High accumulation of platinum-DNA adducts in strial marginal cells of the cochlea is an early event in cisplatin but not carboplatin ototoxicity. Mol Pharmacol 2006; 70 (01) 23-29
  • 27 Deng Y, Xu ZF, Liu W, Xu B, Yang HB, Wei YG. Riluzole-triggered GSH synthesis via activation of glutamate transporters to antagonize methylmercury-induced oxidative stress in rat cerebral cortex. Oxid Med Cell Longev 2012; 2012: 534705
  • 28 Choi BM, Kim SM, Park TK. , et al. Piperine protects cisplatin-induced apoptosis via heme oxygenase-1 induction in auditory cells. J Nutr Biochem 2007; 18 (09) 615-622
  • 29 Li G, Sha SH, Zotova E, Arezzo J, Van de Water T, Schacht J. Salicylate protects hearing and kidney function from cisplatin toxicity without compromising its oncolytic action. Lab Invest 2002; 82 (05) 585-596
  • 30 So HS, Kim HJ, Lee JH. , et al. Flunarizine induces Nrf2-mediated transcriptional activation of heme oxygenase-1 in protection of auditory cells from cisplatin. Cell Death Differ 2006; 13 (10) 1763-1775
  • 31 Hafidi A, Dulon D. Developmental expression of Ca(v)1.3 (α1d) calcium channels in the mouse inner ear. Brain Res Dev Brain Res 2004; 150 (02) 167-175
  • 32 Layton MG, Robertson D, Everett AW, Mulders WH, Yates GK. Cellular localization of voltage-gated calcium channels and synaptic vesicle-associated proteins in the guinea pig cochlea. J Mol Neurosci 2005; 27 (02) 225-244
  • 33 Chen WC, Xue HZ, Hsu Y, Liu Q, Patel S, Davis RL. Complex distribution patterns of voltage-gate calcium channel α-subunits in the spiral ganglion. Hear Res 2011; 278 (1-2): 52-68
  • 34 Hubert JP, Burgevin MC, Terro F, Hugon J, Doble A. Effects of depolarizing stimuli on calcium homeostasis in cultured rat motoneurones. Br J Pharmacol 1998; 125 (07) 1421-1428