[en] Cisplatin is an effective anti-neoplastic agent used in the treatment of squamous cell cancer of the head and neck, but with serious side effects. One serious side effect is damage to both the auditory hair cells and the auditory neurons. The damage to the neurons has been shown to be a direct effect and not due to the loss of the neurotrophic support provided by the hair cells. Several neurotrophins have been shown to lessen the extent of cisplatin induced damage of auditory neurons in vitro, but these neurotrophins have had no effect on the extent of damage to the hair cells. D-methionine (D-met) has been demonstrated to provide protection against cisplatin's nephrotoxicity in vivo and ototoxicity in vitro. In this study the combination of brain derived neurotrophic factor (BDNF) with D-met has shown that both auditory neurons and auditory hair cells can be protected from cisplatin induced damage in vitro. These results demonstrate that this type of combination therapy (i.e. a neurotrophin combined with a free radical scavenger) can provide more complete protection for the auditory receptor against cisplatin toxicity than either of these agents alone. Because both BDNF and D-met have been shown to have trophic activity in vitro we proposed that the combination of these agents will also provide effective protection against cisplatin induced ototoxicity and neurotoxicity of the auditory receptor in vivo.
Van De Water, T.R., Ruben, R.J., A possible embryonic mechanism for the establishment of innervation of inner ear sensory structures (1983) Acta Otolaryngol, 95, pp. 470-479. , Stockh
Zhou, X.-N., Van De Water, T.R., The effect of target tissues on survival and differentiation of mammalian statoacoustic ganglion neurons in organ culture (1987) Acta Otolaryngol, 104, pp. 90-98. , Stockh
Ylikoski, J., Pirvola, U., Moshnyakov, M., Palgi, J., Arumate, U., Saarma, M., Expression patterns of neurotrophins and their receptor mRNAs in the rat inner ear (1993) Hear Res, 65, pp. 69-78
Ernfors, P., Van De Water, T.R., Loring, J., Jaenisch, R., Complementary roles of BDNF and NT-3 in vestibular and auditory development (1995) Neuron, 14, pp. 1153-1164
Zheng, J.L., Stewart, R.R., Gao, W., Neutrotrophin-4/5 enhances survival of cultured spiral ganglion neurons and protects them from cisplatin neurotoxicity (1995) J Neurosci, 15, pp. 5079-5087
Omura, G., Blessing, J.A., Ehrlich, C.E., A randomized trial of cyclophosphamide and doxorubicin with or without cisplatin in advanced ovarian carcinoma (1986) Cancer, 57, pp. 1725-1730
Decker, D.A., Drelichmann, A., Jacobs, J., Adjuvant chemotherapy with cis-diammino-dichloroplatinum II and 120-hour infusion 5-fluorouracil in stage III and IV squamous cell carcinoma of the head and neck (1983) Cancer, 51, pp. 1353-1355
Kopelman, J., Budnick, A.S., Sessions, R.B., Ototoxicity of high-dose cisplatin by bolus administration in patients with advanced cancers and normal hearing (1988) Laryngoscope, 98, pp. 858-864
Schell, M.J., McHaney, V.A., Green, A.A., Hearing loss in children and young adults receiving cisplatin with or without prior cranial irradiation (1989) J Clin Oncol, 7, pp. 754-760
Anniko, M., Sobin, A., Cisplatin: Evaluation of its ototoxic potential (1986) Am J Otol, 7, pp. 276-293
Hinojosa, R., Riggs, L.C., Strauss, M., Temporal bone histopathology of cisplatin ototoxicity (1995) Am J Otol, 16, pp. 731-741
Kopke, R.D., Liu, W., Gabaizadeh, R., The use of organotopic cultures of Corti's organ to study the protective effects of antioxidant molecules in cisplatin induced damage of auditory hair cells (1997) Am J Otology, , in press
Basinger, M.A., Jones, M.M., Holscher, M.A., L-Methionine antagonism of cisplatinum nephrotoxicity (1990) Toxicol Appl Pharmacol, 103, pp. 1-15
Jones, M.M., Basinger, M.A., Holscher, M.A., Control of the nephrotoxicity of cisplatin by clinically used sulfur-containing compounds (1991) Fundam Appl Toxicol, 18, pp. 181-188
Basinger, M.A., Jones, M.M., Holscher, M.A., L-Methionine suppresses pathological sequelae of cisplatinum in the rat (1990) Fundam Appl Toxicol, 14, pp. 568-577
Jones, M.M., Basinger, M.A., Thiol and thioester suppression of cis-platinum-induced nephrotoxicity in rats bearing the Walker 256 carcinosarcoma (1989) Anticancer Res, 9, pp. 1937-1942
Galinovic-Schwartz, V., Peng, D., Chiu, F.C., Van De Water, T.R., Temporal pattern of innervation in the developing mouse inner ear: An immunohistochemical study of a 66-kD subunit of mammalian neurofilaments (1991) J Neurosci Res, 30, pp. 124-133
Lefebvre, P.P., Malgrange, B., Staecker, H., Retinoic acid stimulates regeneration of mammalian auditory hair cells (1993) Science, 260, pp. 692-695
Vogt, W., Oxidation of methionyl residues in proteins: Tools, targets, and reversal (1995) Free Radic Biol Med, 18, pp. 93-105
Harel, S., Kanner, J., The generation of ferryl or hydroxyl radicals during interaction of haemoproteins with hydrogen peroxide (1988) Free Radic Res Commun, 5, pp. 21-33
Appleton, T.G., Connor, J.W., Hall, J.R., S,O-versus S,N-chelation in the reactions of the cis-diamminediaquoplatinum(II) cation with methionine and S-methlycysteine (1988) Inorgan Chem, 27, pp. 130-137
Miller, S.E., House, D.A., The hydrolysis products of cis-dichlorodiammineplatinum(II). 3. Hydrolysis kinetics at physiological pH (1990) Inorgan Chem Acta, 173, pp. 53-60
Hartnick, C.J., Staecker, H., Malgrange, B., Neurotrophic effects of BDNF and CNTF, alone and in combination, on postnatal day 5 rat acoustic ganglion neurons (1996) J Neurobiol Res, 30, pp. 246-254
