Cisplatin, one of the most effective and potent anticancer drugs, is used in the treatment of a wide variety of both pediatric and adult malignancies. However, the chemotherapeutic use of cisplatin is limited by its serious side effects, such as nephrotoxicity and ototoxicity. Ototoxicity produced by cisplatin is usually persistent, depending on the age of the patient, the cumulative number of doses, the number of chemotherapy cycles, the history of noise exposure, and deteriorating renal function. The mechanism of the ototoxicity caused by cisplatin is based on the generation of reactive oxygen species, which interfere with the antioxidant protection of the organ of Corti. Thus, protecting the cochlea with antioxidants ameliorates ototoxicity from cisplatin. In this context, melatonin appears as a therapeutic option for preventing the ototoxic effects of cisplatin, since the research in the last decade has proven its ability to be both a direct free radical scavenger and indirect antioxidant. In this sense, some of the evidence suggesting that melatonin is efficient for combating cisplatin-induced ototoxicity is summarized and discussed in this paper. 1. Introduction Cisplatin is an antineoplastic drug widely used in the treatment of various types of cancer, mainly solid tumors like testicular, ovarian, lung, head, and neck cancers. Nevertheless, its collateral effects, such as nephrotoxicity, neurotoxicity, and ototoxicity, limit its use. Some of these side effects, such as ototoxicity, are dose dependent and this fact prohibits the use of higher doses, which could maximize its antineoplastic activity. While the nephrotoxicity can be diminished or controlled with hydration therapy and diuretics, ototoxicity still remains without an effective treatment. In the last year, many drugs have been studied in an attempt to reduce the cochlear damage induced by cisplatin. Cisplatin-induced ototoxicity is usually manifested by bilateral, progressive, and usually irreversible sensorineural hearing loss, initially occurring in the higher frequencies since cisplatin primarily damages outer hair cells from the basal turn of cochlea and the spiral ganglion neurons [1]. Although ototoxicity caused by cisplatin may occur within hours to days after drug administration, delayed ototoxicity from cisplatin may occur in children [1]. Approximately 23–54% of adults and 45% of pediatric patients with head and neck cancer treated with cisplatin develop ototoxicity [2]. There are several risk factors to cisplatin-induced hearing loss, among which are cumulative doses, age,
References
[1]
L. P. Rybak, D. Mukherjea, S. Jajoo, and V. Ramkumar, “Cisplatin ototoxicity and protection: clinical and experimental studies,” Tohoku Journal of Experimental Medicine, vol. 219, no. 3, pp. 177–186, 2009.
[2]
R. Ravi, S. M. Somani, and L. P. Rybak, “Mechanism of cisplatin ototoxicity: antioxidant system,” Pharmacology & Toxicology, vol. 76, no. 6, pp. 386–394, 1995.
[3]
C. Bokemeyer, C. C. Berger, J. T. Hartmann et al., “Analysis of risk factors for cisplatin-induced ototoxicity in patients with testicular cancer,” British Journal of Cancer, vol. 77, no. 8, pp. 1355–1362, 1998.
[4]
L. P. Rybak, “Mechanisms of cisplatin ototoxicity and progress in otoprotection,” Current Opinion in Otolaryngology and Head and Neck Surgery, vol. 15, no. 5, pp. 364–369, 2007.
[5]
L. P. Rybak, K. Husain, C. Morris, C. Whitworth, and S. Somani, “Effect of protective agents against cisplatin ototoxicity,” The American Journal of Otology, vol. 21, no. 4, pp. 513–520, 2000.
[6]
L. Riedemann, C. Lanvers, D. Deuster et al., “Megalin genetic polymorphisms and individual sensitivity to the ototoxic effect of cisplatin,” Pharmacogenomics Journal, vol. 8, no. 1, pp. 23–28, 2008.
[7]
H.-J. Kim, G.-S. Oh, J.-H. Lee et al., “Cisplatin ototoxicity involves cytokines and STAT6 signaling network,” Cell Research, vol. 21, no. 6, pp. 944–956, 2011.
[8]
A. Ekborn, Cisplatin-induced ototoxicity. Pharmacokinetics, prediction and prevention, 2003.
[9]
C. M. Franceschi de, T. Tochetto, A. F. Silveira Da, M. R. Fantinel, and T. D. Algarve, “Cisplatin effects on guinea pigs: cochlear histology and genotoxicity,” Brazilian Journal of Otorhinolaryngology, vol. 77, no. 6, pp. 728–735, 2011.
[10]
R. J. Reiter, D. X. Tan, L. C. Manchester, M. Pilar Terron, L. J. Flores, and S. Koppisepi, “Medical implications of melatonin: receptor-mediated and receptor-independent actions,” Advances in Medical Sciences, vol. 52, pp. 11–28, 2007.
[11]
M. A. Lopez-Gonzalez, J. M. Guerrero, F. Rojas, and F. Delgado, “Ototoxicity caused by cisplatin is ameliorated by melatonin and other antioxidants,” Journal of Pineal Research, vol. 28, no. 2, pp. 73–80, 2000.
[12]
R. J. Reiter, D. Tan, R. M. Sainz, J. C. Mayo, and S. Lopez-Burillo, “Melatonin: reducing the toxicity and increasing the efficacy of drugs,” Journal of Pharmacy and Pharmacology, vol. 54, no. 10, pp. 1299–1321, 2002.
[13]
J.-H. Kim, S.-J. Jeong, B. Kim, S.-M. Yun, D. Y. Choi, and S.-H. Kim, “Melatonin synergistically enhances cisplatin-induced apoptosis via the dephosphorylation of ERK/p90 ribosomal S6 kinase/heat shock protein 27 in SK-OV-3 cells,” Journal of Pineal Research, vol. 52, no. 2, pp. 244–252, 2014.
[14]
P. Lissoni, S. Barni, M. Mandalà et al., “Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status,” European Journal of Cancer, vol. 35, no. 12, pp. 1688–1692, 1999.
[15]
A. Gonzalez, A. del Castillo-Vaquero, A. Miro-Moran, J. A. Tapia, and G. M. Salido, “Melatonin reduces pancreatic tumor cell viability by altering mitochondrial physiology,” Journal of Pineal Research, vol. 50, no. 3, pp. 250–260, 2011.
[16]
A. Galano, D. X. Tan, and R. J. Reiter, “Melatonin as a natural ally against oxidative stress: a physicochemical examination,” Journal of Pineal Research, vol. 51, no. 1, pp. 1–16, 2011.
[17]
J. Fukutomi, A. Fukuda, S. Fukuda, M. Hara, A. Terada, and M. Yoshida, “Scavenging activity of indole compounds against cisplatin-induced reactive oxygen species,” Life Sciences, vol. 80, no. 3, pp. 254–257, 2006.
[18]
D.-X. Tan, L. C. Manchester, M. P. Terron, L. J. Flores, and R. J. Reiter, “One molecule, many derivatives: a never-ending interaction of melatonin with reactive oxygen and nitrogen species?” Journal of Pineal Research, vol. 42, no. 1, pp. 28–42, 2007.
[19]
L.-F. Ye, Z.-Z. Tao, Q.-Q. Hua, et al., “Protective effect of melatonin against gentamicin ototoxicity,” The Journal of Laryngology & Otology, vol. 123, no. 6, pp. 598–602, 2009.
[20]
C. Rodriguez, J. C. Mayo, R. M. Sainz, et al., “Regulation of antioxidant enzymes: a significant role for melatonin,” Journal of Pineal Research, vol. 36, no. 1, pp. 1–9, 2004.
[21]
J. Espino, J. A. Pariente, and A. B. Rodríguez, “Oxidative stress and immunosenescence: therapeutic effects of melatonin,” Oxidative Medicine and Cellular Longevity, vol. 2012, Article ID 670294, 9 pages, 2012.
[22]
M. Karasek, “Melatonin, human aging, and age-related diseases,” Experimental Gerontology, vol. 39, no. 11-12, pp. 1723–1729, 2004.
[23]
R. J. Reiter, D. Tan, J. C. Mayo, R. M. Sainz, J. Leon, and Z. Czarnocki, “Melatonin as an antioxidant: biochemical mechanisms and pathophysiological implications in humans,” Acta Biochimica Polonica, vol. 50, no. 4, pp. 1129–1146, 2003.
[24]
L. Lin, Q.-X. Huang, S.-S. Yang, J. Chu, J.-Z. Wang, and Q. Tian, “Melatonin in Alzheimer’s disease,” International Journal of Molecular Sciences, vol. 14, no. 7, pp. 14575–14593, 2013.
[25]
J. M. Olcese, C. Cao, T. Mori et al., “Protection against cognitive deficits and markers of neurodegeneration by long-term oral administration of melatonin in a transgenic model of Alzheimer disease,” Journal of Pineal Research, vol. 47, no. 1, pp. 82–96, 2009.
[26]
J. Z. Wang and Z. F. Wang, “Role of melatonin in Alzheimer-like neurodegeneration,” Acta Pharmacologica Sinica, vol. 27, no. 1, pp. 41–49, 2006.
[27]
V. Srinivasan, D. P. Cardinali, U. S. Srinivasan et al., “Therapeutic potential of melatonin and its analogs in Parkinson's disease: focus on sleep and neuroprotection,” Therapeutic Advances in Neurological Disorders, vol. 4, no. 5, pp. 297–317, 2011.
[28]
L. Lin, Y. Du, S. Yuan, J. Shen, X. Lin, and Z. Zheng, “Serum melatonin is an alternative index of Parkinson’s disease severity,” Brain Research, vol. 1547, pp. 43–48, 2014.
[29]
G. Rocchitta, R. Migheli, G. Esposito et al., “Endogenous melatonin protects L-DOPA from autoxidation in the striatal extracellular compartment of the freely moving rat: potential implication for long-term L-DOPA therapy in Parkinson's disease,” Journal of Pineal Research, vol. 40, no. 3, pp. 204–213, 2006.
[30]
E. Gitto, M. Karbownik, R. J. Reiter et al., “Effects of melatonin treatment in septic newborns,” Pediatric Research, vol. 50, no. 6, pp. 756–760, 2001.
[31]
A. M. Sánchez-Sánchez, V. Martín, G. García-Santos et al., “Intracellular redox state as determinant for melatonin antiproliferative vs cytotoxic effects in cancer cells,” Free Radical Research, vol. 45, no. 11-12, pp. 1333–1341, 2011.
[32]
R. M. Sainz, J. C. Mayo, C. Rodriguez, D. X. Tan, S. Lopez-Burillo, and R. J. Reiter, “Melatonin and cell death: differential actions on apoptosis in normal and cancer cells,” Cellular and Molecular Life Sciences, vol. 60, no. 7, pp. 1407–1426, 2003.
[33]
S. Cos, A. González, C. Martínez-Campa, M. D. Mediavilla, C. Alonso-González, and E. J. Sánchez-Barceló, “Estrogen-signaling pathway: a link between breast cancer and melatonin oncostatic actions,” Cancer Detection and Prevention, vol. 30, no. 2, pp. 118–128, 2006.
[34]
A. N. Viswanathan and E. S. Schernhammer, “Circulating melatonin and the risk of breast and endometrial cancer in women,” Cancer Letters, vol. 281, no. 1, pp. 1–7, 2009.
[35]
S. M. Hill, T. Frasch, and T. Duplessis, “Molecular mechanisms of melatonin anticancer effects,” Integrative Cancer Therapies, vol. 8, no. 4, pp. 337–346, 2009.
[36]
A. Korkmaz, E. J. Sanchez-Barcelo, D. X. Tan, and R. J. Reiter, “Role of melatonin in the epigenetic regulation of breast cancer,” Breast Cancer Research and Treatment, vol. 115, no. 1, pp. 13–27, 2009.
[37]
N. Song, A. J. Kim, H. Kim et al., “Melatonin suppresses doxorubicin-induced premature senescence of A549 lung cancer cells by ameliorating mitochondrial dysfunction,” Journal of Pineal Research, vol. 53, no. 4, pp. 335–343, 2012.
[38]
P. Lissoni, M. Chilelli, S. Villa, L. Cerizza, and G. Tancini, “Five years survival in metastatic non-small cell lung cancer patients treated with chemotherapy alone or chemotherapy and melatonin: a randomized trial,” Journal of Pineal Research, vol. 35, no. 1, pp. 12–15, 2003.
[39]
S. Casado-Zapico, V. Martín, G. García-Santos, et al., “Regulation of the expression of death receptors and their ligands by melatonin in haematological cancer cell lines and in leukaemia cells from patients,” Journal of Pineal Research, vol. 50, no. 3, pp. 345–355, 2011.
[40]
I. Bejarano, P. C. Redondo, J. Espino et al., “Melatonin induces mitochondrial-mediated apoptosis in human myeloid HL-60 cells,” Journal of Pineal Research, vol. 46, no. 4, pp. 392–400, 2009.
[41]
O. Trubiani, R. Recchioni, F. Moroni, J. Pizzicannella, S. Caputi, and R. di Primio, “Melatonin provokes cell death in human B-lymphoma cells by mitochondrial-dependent apoptotic pathway activation,” Journal of Pineal Research, vol. 39, no. 4, pp. 425–431, 2005.
[42]
S. Rubio, F. Estévez, J. Cabrera, R. J. Reiter, J. Loro, and J. Quintana, “Inhibition of proliferation and induction of apoptosis by melatonin in human myeloid HL-60 cells,” Journal of Pineal Research, vol. 42, no. 2, pp. 131–138, 2007.
[43]
G. García-Santos, I. Antolín, F. Herrera, V. Martín, J. Rodriguez-Blanco, and M. del Pilar Carrera, “Melatonin induces apoptosis in human neuroblastoma cancer cells,” Journal of Pineal Research, vol. 41, no. 2, pp. 130–135, 2006.
[44]
V. Martín, G. García-Santos, J. Rodriguez-Blanco, et al., “Melatonin sensitizes human malignant glioma cells against TRAIL-induced cell death,” Cancer Letters, vol. 287, no. 2, pp. 216–223, 2010.
[45]
V. Martín, F. Herrera, P. Carrera-Gonzalez et al., “Intracellular signaling pathways involved in the cell growth inhibition of glioma cells by melatonin,” Cancer Research, vol. 66, no. 2, pp. 1081–1088, 2006.
[46]
J. Wang, H. Hao, L. Yao et al., “Melatonin suppresses migration and invasion via inhibition of oxidative stress pathway in glioma cells,” Journal of Pineal Research, vol. 53, no. 2, pp. 180–187, 2012.
[47]
S. Casado-Zapico, J. Rodriguez-Blanco, G. García-Santos, et al., “Synergistic antitumor effect of melatonin with several chemotherapeutic drugs on human Ewing sarcoma cancer cells: potentiation of the extrinsic apoptotic pathway,” Journal of Pineal Research, vol. 48, no. 1, pp. 72–80, 2014.
[48]
G. García-Santos, V. Martin, J. Rodríguez-Blanco, et al., “Fas/Fas ligand regulation mediates cell death in human Ewings sarcoma cells treated with melatonin,” British Journal of Cancer, vol. 106, no. 7, pp. 1288–1296, 2012.
[49]
B. H. Ali and M. S. Al Moundhri, “Agents ameliorating or augmenting the nephrotoxicity of cisplatin and other platinum compounds: a review of some recent research,” Food and Chemical Toxicology, vol. 44, no. 8, pp. 1173–1183, 2006.
[50]
M. Hara, M. Yoshida, H. Nishijima et al., “Melatonin, a pineal secretory product with antioxidant properties, protects against cisplatin-induced nephrotoxicity in rats,” Journal of Pineal Research, vol. 30, no. 3, pp. 129–138, 2001.
[51]
G. Sener, L. Kabasakal, S. Arbakb, S. Onerb, F. Ercanb, and M. K. Uysal, “The protective effect of melatonin on cisplatin nephrotoxicity,” Fundamental & Clinical Pharmacology, vol. 14, pp. 553–560, 2000.
[52]
U. Kilic, E. Kilic, Z. Tuzcu, et al., “Melatonin suppresses cisplatin-induced nephrotoxicity via activation of Nrf-2/HO-1 pathway,” Nutrition & Metabolism, vol. 10, no. 1, article 7, 2013.
[53]
H. Parlakpinar, E. Sahna, M. K. Ozer, F. Ozugurlu, N. Vardi, and A. Acet, “Physiological and pharmacological concentrations of melatonin protect against cisplatin-induced acute renal injury,” Journal of Pineal Research, vol. 33, no. 3, pp. 161–166, 2002.
[54]
K. E. Atalik, B. Kele？, Y. Uyar, M. A. Dündar, M. Oz, and H. H. Esen, “Vasoprotection by melatonin and quercetin in rats treated with cisplatin,” Indian Journal of Experimental Biology, vol. 48, no. 12, pp. 1188–1193, 2010.
[55]
Y. O. Ilbey, E. Ozbek, A. Simsek, A. Otunctemur, M. Cekmen, and A. Somay, “Potential chemoprotective effect of melatonin in cyclophosphamide- and cisplatin-induced testicular damage in rats,” Fertility and Sterility, vol. 92, no. 3, pp. 1124–1132, 2009.
[56]
A. Ate？？ahin, E. Sahna, G. Türk, et al., “Chemoprotective effect of melatonin against cisplatin-induced testicular toxicity in rats,” Journal of Pineal Research, vol. 41, no. 1, pp. 21–27, 2006.
[57]
M. A. Lopez-Gonzalez, J. M. Guerrero, R. Torronteras, C. Osuna, and F. Delgado, “Ototoxicity caused by aminoglycosides is ameliorated by melatonin without interfering with the antibiotic capacity of the drugs,” Journal of Pineal Research, vol. 28, no. 1, pp. 26–33, 2000.
[58]
O. W. Guthrie, “Aminoglycoside induced ototoxicity,” Toxicology, vol. 249, no. 2-3, pp. 91–96, 2008.
[59]
J.-B. Kim, J. Y. Jung, J.-C. Ahn, C. K. Rhee, and H. Hwang, “Antioxidant and anti-apoptotic effect of melatonin on the vestibular hair cells of rat utricles,” Clinical and Experimental Otorhinolaryngology, vol. 2, no. 1, pp. 6–12, 2009.
[60]
E. Bas, T. R. Van De Water, C. Gupta, et al., “Efficacy of three drugs for protecting against gentamicin-induced hair cell and hearing losses,” British Journal of Pharmacology, vol. 166, no. 6, pp. 1888–1904, 1888.
[61]
T. Erdem, O. Ozturan, M. Iraz, M. C. Miman, and E. Olmez, “Dose-dependent dual effect of melatonin on ototoxicity induced by amikacin in adult rats,” European Archives of Oto-Rhino-Laryngology, vol. 262, no. 4, pp. 314–321, 2005.
[62]
J. G. Kalkanis, C. Whitworth, and L. P. Rybak, “Vitamin E reduces cisplatin ototoxicity,” Laryngoscope, vol. 114, no. 3, pp. 538–542, 2004.
[63]
S. A. Tokg？z, E. Vuralkan, N. D. Sonbay, et al., “Protective effects of vitamins E, B and C and L-carnitine in the prevention of cisplatin-induced ototoxicity in rats,” The Journal of Laryngology & Otology, vol. 126, no. 5, pp. 464–469, 2012.
[64]
G. Sim？ek, S. A. Tokgoz, E. Vuralkan, M. Caliskan, O. Besalti, and I. Akin, “Protective effects of resveratrol on cisplatin-dependent inner-ear damage in rats,” European Archives of Oto-Rhino-Laryngology, vol. 270, no. 6, pp. 1789–1793, 2013.
[65]
T. Erdem, T. Bayindir, A. Filiz, M. Iraz, and E. Selimoglu, “The effect of resveratrol on the prevention of cisplatin ototoxicity,” European Archives of Oto-Rhino-Laryngology, vol. 269, no. 10, pp. 2185–2188, 2012.
[66]
A. L. L. Sampaio, M. A. Dias, A. R. Venosa, P. L. Tauil, E. Alencar, and C. A. C. P. Oliveira, “The Effect of Gingko Biloba (EGB 761) as an otoprotector against cisplatin ototoxicity,” Otolaryngology—Head and Neck Surgery, vol. 149, supplement 2, pp. P222–P223, 2013.
[67]
B. A. Abdel-Wahab and S. M. Abd El-Aziz, “Ginkgo biloba protects against intermittent hypoxia-induced memory deficits and hippocampal DNA damage in rats,” Phytomedicine, vol. 19, no. 5, pp. 444–450, 2012.
[68]
X. Huang, C. A. Whitworth, and L. P. Rybak, “Ginkgo Biloba extract (EGb 761) protects against cisplatin-induced ototoxicity in rats,” Otology & Neurotology, vol. 28, no. 6, pp. 828–833, 2007.
[69]
S. J. Choi, S. W. Kim, J. B. Lee et al., “Gingko biloba extracts protect auditory hair cells from cisplatin-induced ototoxicity by inhibiting perturbation of gap junctional intercellular communication,” Neuroscience, vol. 244, pp. 49–61, 2013.
[70]
M. A. Hyppolito, M. Rossato, and F. Holanda, “Ototoxicidade da cisplatina e otoprote？？o pelo extrato de ginkgo biloba às células ciliadas externas: estudo anat？mico e eletrofisiol？gico,” Brazilian Journal of Otorhinolaryngology, vol. 69, no. 4, pp. 504–511, 2003.
[71]
C. J. Tian, Y. J. Kim, S. W. Kim, H. J. Lim, Y. S. Kim, and Y.-H. Choung, “A combination of cilostazol and Ginkgo biloba extract protects against cisplatin-induced Cochleo-vestibular dysfunction by inhibiting the mitochondrial apoptotic and ERK pathways,” Cell Death and Disease, vol. 4, no. 2, p. e509, 2013.
[72]
S. J. Hong, G. J. Im, J. Chang, et al., “Protective effects of edaravone against cisplatin-induced hair cell damage in zebrafish,” International Journal of Pediatric Otorhinolaryngology, vol. 77, no. 6, pp. 1025–1031, 2013.
[73]
O. Kuduban, C. Kucur, E. Sener, H. Suleyman, and F. Akcay, “The role of thiamine pyrophosphate in prevention of cisplatin ototoxicity in an animal model,” The Scientific World Journal, vol. 2013, Article ID 182694, 5 pages, 2013.
[74]
G. Lorito, S. Hatzopoulos, G. Laurell, et al., “Dose-dependent protection on cisplatin-induced ototoxicity—an electrophysiological study on the effect of three antioxidants in the Sprague-Dawley rat animal model,” Medical Science Monitor, vol. 17, no. 8, pp. BR179–BR186, 2011.
[75]
K. C. M. Campbell, R. P. Meech, L. P. Rybak, and L. F. Hughes, “The effect of D-methionine on cochlear oxidative state with and without cisplatin administration: mechanisms of otoprotection,” Journal of the American Academy of Audiology, vol. 14, no. 3, pp. 144–156, 2003.
[76]
K. D. Korver, L. P. Rybak, C. Whitworth, and K. M. Campbell, “Round window application of D-methionine provides complete cisplatin otoprotection,” Otolaryngology—Head and Neck Surgery, vol. 126, no. 6, pp. 683–689, 2002.
[77]
M. G. Riga, L. Chelis, S. Kakolyris et al., “Transtympanic injections of N-acetylcysteine for the prevention of cisplatin-induced ototoxicity: a feasible method with promising efficacy,” The American Journal of Clinical Oncology: Cancer Clinical Trials, vol. 36, no. 1, pp. 1–6, 2013.
[78]
H. J. Jeong, Y. Choi, M. H. Kim et al., “Rosmarinic acid, active component of dansam-eum attenuates ototoxicity of cochlear hair cells through blockage of caspase-1 activity,” PLoS ONE, vol. 6, no. 4, Article ID e18815, 2011.
[79]
S. Celebi, M. M. Gurdal, M. H. Ozkul, H. Yasar, and H. H. Balikci, “The effect of intratympanic vitamin C administration on cisplatin-induced ototoxicity,” European Archives of Oto-Rhino-Laryngology, vol. 270, no. 4, pp. 1293–1297, 2013.
[80]
M. Paksoy, E. Ayduran, A. Sanl？, M. Eken, S. Aydin, and Z. A. Oktay, “The protective effects of intratympanic dexamethasone and vitamin E on cisplatin-induced ototoxicity are demonstrated in rats,” Medical Oncology, vol. 28, no. 2, pp. 615–621, 2011.
[81]
D. Murphy and S. J. Daniel, “Intratympanic dexamethasone to prevent cisplatin ototoxicity: a guinea pig model,” Otolaryngology: Head and Neck Surgery, vol. 145, no. 3, pp. 452–457, 2011.
[82]
A. G. Shafik, R. H. Elkabarity, M. T. Thabet, N. B. Soliman, and N. K. Kalleny, “Effect of intratympanic dexamethasone administration on cisplatin-induced ototoxicity in adult guinea pigs,” Auris Nasus Larynx, vol. 40, no. 1, pp. 51–60, 2013.
[83]
G. W. Hill, D. K. Morest, and K. Parham, “Cisplatin-induced ototoxicity: effect of intratympanic dexamethasone injections,” Otology & Neurotology, vol. 29, no. 7, pp. 1005–1011, 2008.
