Cisplatine bağlı gelişen ototoksisitenin N-asetilsistein ve salisilat ile önlenmesi

Amaç: Bu çalışmada salisilat ve N-asetilsistein kullanımıyla cisplatin kaynaklı ototoksisitenin azaltılabilirliği ya da engellenebilirliği araştırıldı.Hastalar ve Yöntemler: Solid organ tümörü nedeniyle cisplatin kemoterapi kullanan 54 hasta 28 kadın, 26 erkek; ort. yaş 37±9.5; dağılım 29-71 yıl çalışmaya dahil edildi. Hastalar her bir grupta 18 kişi olacak şekilde rastgele üç gruba ayrıldı. İlk grup kontrol grubu sadece cisplatin aldı, ikinci grup N-acetylcysteine NAC; 600 mg/gün ile birlikte cisplatin aldı ve üçüncü grup salisilat 300 mg/gün ile birlikte cisplatin aldı. Bütün hastalar yüksek frekans odyometri ve işitsel beyin sapı yanıtını içeren odyolojik incelemeyle değerlendirildi.Bulgular: Cisplatin tedavi protokolüne N-asetilsisteine eklenmesiyle, 10.000 ve 12.000 Hz frekanslarındaki cisplatin kaynaklı ototoksik hasarın azaldığı görüldü. Cisplatine ile salisilat alan hastaların işitme kayıbı seviyelerinde herhangi bir azalma görülmedi.Sonuç: Çalışmamızda işitsel beyin sapı yanıtı testi sonuçlarına bakıldığında ne N-asetilsistein ne de salisilat alan hastalar arasında cisplatin ototoksisitesini azaltma yönünden anlamlı fark bulundu

Preventing cisplatin induced ototoxicity by N-acetylcysteine and salicylate

Objectives: In this study we investigated if CP induced ototoxicity could be prevented or reduced by the use of salicylate and N-acetylcysteine. Patients and Methods: Fifty-four patients 28 females, 26 males; mean age 37±9.5 years; range 29 to 71 years who had cisplatin chemotherapy due to solid organ tumors were enrolled in the study. The patients were randomized into three groups, with 18 patients in each group. The first group control group received cisplatin, second group received N-acetylcysteine NAC; 600 mg/day with cisplatin and the third group received salicylate 300 mg/day with cisplatin. All patients evaluated audiologically including high frequency audiometry and auditory brainstem response. Results: The cisplatin-induced ototoxic damage could be reduced in 10,000 and 12,000 Hz frequencies when N-acetylcysteine was added to the cisplatin therapy protocol. There was no decrease in the hearing loss levels of the patients who were receiving cisplatin with salicylate. Conclusion: According to auditory brainstem response testing results, there was no difference detected between N-acetylcysteine or salicylate for the amelioration of cisplatin induced ototoxicity.

___

  • Stocks RM, Gould HJ, Bush AJ, Dudney BW Jr, Pousson M, Thompson JW. Ototoxic protection of sodium thio- sulfate: daily vs constant infusion. Otolaryngol Head Neck Surg 2004;131:115-9.
  • Mom T, Avan P, Romand R, Gilain L. Monitoring of functional changes after transient ischemia in gerbil cochlea. Brain Res 1997;751:20-30.
  • Comis SD, Rhys-Evans PH, Osborne MP, Pickles JO, Jeffries DJ, Pearse HA. Early morphological and chemical changes induced by cisplatin in the guinea pig organ of Corti. J Laryngol Otol 1986;100:1375-83.
  • Schweitzer VG. Cisplatin-induced ototoxicity: the effect of pigmentation and inhibitory agents. Laryngoscope 1993;103:1-52.
  • Kingston JE, Abramovich S, Billings RJ, Malpas JS, Fuller AP. Assessment of the effect of chemotherapy and radiotherapy on the auditory function of children with cancer. Clin Otolaryngol Allied Sci 1986;11:403-9.
  • Rybak LP, Whitworth CA, Mukherjea D, Ramkumar V. Mechanisms of cisplatin-induced ototoxicity and prevention. Hear Res 2007;226:157-67.
  • Yorgason JG, Fayad JN, Kalinec F. Understanding drug ototoxicity: molecular insights for prevention and clini- cal management. Expert Opin Drug Saf 2006;5:383-99.
  • Coradini PP, Cigana L, Selistre SG, Rosito LS, Brunetto AL. Ototoxicity from cisplatin therapy in childhood cancer. J Pediatr Hematol Oncol 2007;29:355-60.
  • Giordano P, Lorito G, Ciorba A, Martini A, Hatzopoulos S. Protection against cisplatin ototoxicity in a Sprague- Dawley rat animal model. Acta Otorhinolaryngol Ital 2006;26:198-207.
  • Tange RA, Dreschler WA, van der Hulst RJ. The importance of high-tone audiometry in monitoring for ototoxicity. Arch Otorhinolaryngol 1985;242:77-81.
  • De Lauretis A, De Capua B, Barbieri MT, Bellussi L, Passàli D. ABR evaluation of ototoxicity in can- cer patients receiving cisplatin or carboplatin. Scand Audiol 1999;28:139-43.
  • Scarpace SL, Brodzik FA, Mehdi S, Belgam R. Treatment of head and neck cancers: issues for clinical pharma- cists. Pharmacotherapy 2009;29:578-92.
  • Park KR. The utility of acoustic reflex thresholds and other conventional audiologic tests for monitoring cis- platin ototoxicity in the pediatric population. Ear Hear 1996;17:107-15.
  • Hyppolito MA, de Oliveira JA, Rossato M. Cisplatin ototoxicity and otoprotection with sodium salicylate. Eur Arch Otorhinolaryngol 2006;263:798-803.
  • Rybak LP, Somani S. Ototoxicity. Amelioration by pro- tective agents. Ann N Y Acad Sci 1999;884:143-51.
  • Bulut E, Yağiz R, Taş A, Uzun C, Yildirim C, Kaymak K, et al. Evaluation of the protective effect of magne- sium on amikacin ototoxicity by electrophysiologic tests in guinea pigs. [Article in Turkish] Kulak Burun Bogaz Ihtis Derg 2005;15:70-7.
  • Daldal A, Odabasi O, Serbetcioglu B. The protective effect of intratympanic dexamethasone on cisplatin- induced ototoxicity in guinea pigs. Otolaryngol Head Neck Surg 2007;137:747-52.
  • Sahin AA, Oysu C, Yilmaz HB, Topak M, Kulekci M, Okar I. Effect of oral magnesium supplementation on cisplatin ototoxicity. J Otolaryngol 2006;35:112-6.
  • Iraz M, Kalcioglu MT, Kizilay A, Karatas E. Aminoguanidine prevents ototoxicity induced by cis- platin in rats. Ann Clin Lab Sci 2005;35:329-35.
  • Kalcioglu MT, Kizilay A, Gulec M, Karatas E, Iraz M, Akyol O, et al. The protective effect of erdosteine against ototoxicity induced by cisplatin in rats. Eur Arch Otorhinolaryngol 2005;262:856-63.
  • Güneri EA, Serbetçioğlu B, Ikiz AO, Güneri A, Ceryan K. TEOAE monitoring of Cisplatin induced ototoxicity in guinea pigs: the protective effect of vitamin B treat- ment. Auris Nasus Larynx 2001;28:9-14.
  • Kizilay A, Kalcioglu MT, Ozerol E, Iraz M, Gulec M, Akyol O, et al. Caffeic acid phenethyl ester ameliorated ototoxicity induced by cisplatin in rats. J Chemother 2004;16:381-7.
  • Ekborn A, Laurell G, Ehrsson H, Miller J. Intracochlear administration of thiourea protects against cisplatin- induced outer hair cell loss in the guinea pig. Hear Res 2003;181:109-15.
  • Blakley BW, Hochman J, Wellman M, Gooi A, Hussain AE. Differences in Ototoxicity across Species. J Otolaryngol Head Neck Surg 2008;37:700-3.
  • Vaughan NE, Fausti SA, Chelius S, Phillips D, Helt W, Henry JA. An efficient test protocol for identification of a limited, sensitive frequency test range for early detec- tion of ototoxicity. J Rehabil Res Dev 2002;39:567-74.
  • Jacob LC, Aguiar FP, Tomiasi AA, Tschoeke SN, Bitencourt RF. Auditory monitoring in ototoxicity. Braz J Otorhinolaryngol 2006;72:836-44.
  • Fausti SA, Frey RH, Henry JA, Olson DJ, Schaffer HI. High-frequency testing techniques and instrumenta- tion for early detection of ototoxicity. J Rehabil Res Dev 1993;30:333-41.
  • Tsukimura N, Yamada M, Aita H, Hori N, Yoshino F, Chang-Il Lee M, et al. N-acetyl cysteine (NAC)- mediated detoxification and functionalization of poly(methyl methacrylate) bone cement. Biomaterials 2009;30:3378-89.
  • Lamson DW, Brignall MS. Antioxidants in cancer therapy; their actions and interactions with oncologic therapies. Altern Med Rev 1999;4:304-29.
  • Wu YJ, Muldoon LL, Neuwelt EA. The chemoprotec- tive agent N-acetylcysteine blocks cisplatin-induced apoptosis through caspase signaling pathway. J Pharmacol Exp Ther 2005;312:424-31.
  • Dickey DT, Wu YJ, Muldoon LL, Neuwelt EA. Protection against cisplatin-induced toxicities by N-acetylcysteine and sodium thiosulfate as assessed at the molecular, cellular, and in vivo levels. J Pharmacol Exp Ther 2005;314:1052-8.
  • Rybak LP, Whitworth C, Somani S. Application of antioxidants and other agents to prevent cisplatin oto- toxicity. Laryngoscope 1999;109:1740-4.
  • Campbell KC, Meech RP, Rybak LP, Hughes LF. The effect of D-methionine on cochlear oxidative state with and without cisplatin administration: mechanisms of otoprotection. J Am Acad Audiol 2003;14:144-56.