Koenzim Q10’un ratlarda sıçanlarda sisplatinin neden olduğu ototoksisiteye etkisi

Abstract

Objective: To determine the efficacy of systemic administration of coenzyme Q10 at low and high doses on cisplatin-induced ototoxicity in rats.
Methods: Our study was performed with 40 Sprague-Dawley rats. They were divided randomly into five groups: Cis, Cis+Q1030, Cis+Q1010, Q10, and control. Cis (n=8) group was administered cisplatin [a single intraperitoneal (i.p.) injection of 14 mg/kg], Cis+Q1030 (n=8) group was administered cisplatin (a single i.p. injection of 14 mg/kg) and
coenzyme Q10 (30 mg/kg/day, i.p.) for 3 days, Cis+Q1010 (n=8) group was given cisplatin (a single dose of 14 mg/kg/day, i.p.) and coenzyme Q10 (10 mg/kg/day, i.p.) for 3 days, Q10 (n=8) group was administered coenzyme Q10 (10 mg/kg/day, i.p.) for 3 days and Group C (n=8) (control group) was administered saline solution (1 mL/day, i.p.) once daily for 3 days. Pretreatment and posttreatment hearing levels were evaluated with distortion product otoacoustic emissions (DPOAEs).
Results: There was no statistically significant difference in the results of measurements of 4004, 4358, 4761 and 5188 Hz at end of the study in comparison to baseline (p>0.05). On the other hand, there was a significant
difference at the measurements of 5652, 6165, 7336 and 7996 Hz (p=0.002, p=0.037, p=0.001, p=0.001, respectively). The rate of change at 5652 Hz revealed that Cis group was different from Cis+Q1010, control and Q10 groups (p<0.01); measurements at 6165 Hz revealed that change at Cis group was significantly different from control and Q10 groups (p<0.01, p<0.05). Final measurements of decrease in Cis group at 7336 and 7996 Hz were significantly different from baseline (p<0.05; p<0.01).
Conclusion: The high-dose coenzyme Q10 showed a protective effect on hearing in cisplatin-induced ototoxicity while low-dose coenzyme Q10 protected hearing at low frequencies but did not show protective effect at high frequencies.

Keywords

• Ototoxicity,cisplatin,coenzyme Q10,rats

References

1. 1. Walker EM Jr, Fazekas-May MA, Bowen WR. Nephrotoxic and ototoxic agents. Clin Lab Med 1990;10:323–54.
2. 2. Ravi R, Somani SM, Rybak LP. Mechanism of cisplatin ototoxicity: antioxidant system. Pharmacol Toxicol 1995;76:386–94.
3. 3. 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.
4. 4. Rybak LP, Whitworth CA, Mukherjea D, Ramkuvar L. Mechanisms of cisplatin-induced ototoxicity and prevention. Hear Res 2007;226:157–67.
5. 5. Van den Berg JH, Beijnen JH, Balm AJ, Schellens JH. Future opportunities in preventing cisplatin induced ototoxicity. Cancer Treat Rev 2006;32:390–7.
6. 6. Fetoni AR, Sergi B, Ferraresi A, Paludetti G, Troiani D. Protective effects of alpha-tocopherol and tiopronin against cisplatin- induced ototoxicity. Acta Otolaryngol 2004;124:421–6.
7. 7. Ise T, Shimizu T, Lee EL, Inoue H, Kohno K, Okada Y. Roles of volume-sensitive Cl-channel in cisplatin-induced apoptosis in human epidermoid cancer cells. J Membr Biol 2005;205:139–45.
8. 8. Van Ruijven MW, de Groot JC, Klis SF, Smoorenbug GF. The cochlear targets of cisplatin: an electrophysiological and morphological time-sequence study. Hear Res 2005;205:241–8.

9. 9. Sergi B, Fetoni AR, Paludetti G, et al. Protective properties of idebenone in noise-induced hearing loss in the guinea pig. Neuroreport 2006;17:857–61.
10. 10. Papucci L, Schiavone N, Witort E, et al. Coenzyme Q10 prevents apoptosis by inhibiting mitochondrial depolarization independently of its free radical scavenging property. J Biol Chem 2003;278: 28220–8.
11. 11. Hinojosa R, Riggs LC, Strauss M, Matz GJ. Temporal bone histopathology of cisplatin ototoxicity. Am J Otol 1995;16:731–40.
12. 12. Hyppolito MA, de Oliveira JA, Rossato M. Cisplatin ototoxicity and otoprotection with sodium salicylate. Eur Arch Otorhinolaryngol 2006;263:798–803.
13. 13. Church MW, Blakley BW, Burgio DL, Gupta AK. WR-2721 (Amifostine) ameliorates cisplatin-induced hearing loss but causes neurotoxicity in hamsters: dose-dependent effects. J Assoc Res Otolaryngol 2004;5:227–37.
14. 14. Korver KD, Rybak LP, Whitworth C, Campbell KM. Round window application of D-methionine provides complete cisplatin otoprotection. Otolaryngol Head Neck Surg 2002;126:683–9.
15. 15. Kalkanis JG, Whitworth C, Rybak LP. Vitamin E reduces cisplatin ototoxicity. Laryngoscope 2004;114:538–42.
16. 16. Berkiten G, Salturk Z, Topalo¤lu I, U¤rafl H. Protective effect of pentoxifylline on amikacin-induced ototoxicity in rats. Am J Otolaryngol 2012;33:689–92.
17. 17. Chen X, Frisina RD, Bowers WJ, Frisina DR, Federoff HJ. HSV amplicon-mediated neurotrophin-3 expression protects murine spiral ganglion neurons from cisplatin-induced damage. Mol Ther 2001;3:958–63.
18. 18. So HS, Park C, Kim HJ, et al. Protective effect of T-type calcium channel blocker flunarizine on cisplatin-induced death of auditory cells. Hear Res 2005;204:127–39.
19. 19. Lopez-Gonzalez MA, Guerrero JM, Rojas F, Delgado F. Ototoxicity caused by cisplatin is ameliorated by melatonin and other antioxidants. J Pineal Res 2000;28:73–80.
20. 20. Rybak LP, Husain K, Morris C, Whitworth C, Somani S. Effect of protective agents against cisplatin ototoxicity. Am J Otol 2000; 21:513–20.
21. 21. Ahn JH, Yoo MH, Lee HJ, Chung JW, Yoon TH. Coenzyme Q10 in combination with steroid therapy for treatment of sudden sensorineural hearing loss: a controlled prospective study. Clin Otolaryngol 2010;35:486–9.
22. 22. Hirose Y, Sugahara K, Mikuriya T, Hashimoto M, Shimogori H, Yamashita H. Effect of water-soluble coenzyme Q10 on noiseinduced hearing loss in guinea pigs. Acta Otolaryngol 2008;128:1071–6.
23. 23. Guastini L, Mora R, Dellepiane M, Santamauro V, Giorgio M, Salami A. Water-soluble coenzyme Q10 formulation in presbycusis: long-term effects. Acta Otolaryngol 2011;131:512–7.
24. 24. Fetoni AR, Eramo SL, Rolesi R, Troiani D, Paludetti G. Antioxidant treatment with coenzyme Q-ter in prevention of gentamycin ototoxicity in an animal model. Acta Otorhinolaryngol Ital 2012;32:103–10.
25. 25. Sockalingam R, Freeman S, Cherny TL, Sohmer T. Effect of high-dose cisplatin on auditory brainstem responses and otoacoustic emissions in laboratory animals. Am J Otol 2000;21:521–7.
26. 26. Fetoni AR, Garzaro M, Ralli M, et al. The monitoring role of otoacoustic emissions and oxidative stress markers in the protective effects of antioxidant administration in noise-exposed subjects: a pilot study. Med Sci Monit 2009;15:PR1–8.