Hostname: page-component-89b8bd64d-9prln Total loading time: 0 Render date: 2026-05-10T20:34:13.206Z Has data issue: false hasContentIssue false
  • English
  • Français

Protective effects of vitamins E, B and C and l-carnitine in the prevention of cisplatin-induced ototoxicity in rats

Published online by Cambridge University Press:  11 April 2012

S Alıcura Tokgöz ,
E Vuralkan ,
N D Sonbay ,
M Çalişkan ,
C Saka ,
Ö Beşalti  and
İ Akin
S Alıcura Tokgöz*
Affiliation:
First ENT Clinic, Ministry of Health Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey
E Vuralkan
Affiliation:
First ENT Clinic, Ministry of Health Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey
N D Sonbay
Affiliation:
First ENT Clinic, Ministry of Health Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey
M Çalişkan
Affiliation:
Faculty of Veterinary Medicine, Ankara University, Turkey
C Saka
Affiliation:
First ENT Clinic, Ministry of Health Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey
Ö Beşalti
Affiliation:
Faculty of Veterinary Medicine, Ankara University, Turkey
İ Akin
Affiliation:
First ENT Clinic, Ministry of Health Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey
*
Address for correspondence: Dr Sibel Alicura Tokgöz, First ENT Clinic, Dışkapı Yldırım Beyazıt Training and Research Hospital, Ministry of Health, Ankara, Turkey E-mail: salicura@yahoo.com
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective:

This experimental study aimed to investigate the effects of vitamins E, B and C and l-carnitine in preventing cisplatin-induced ototoxicity.

Methods:

Twenty-five adult, male, Wistar albino rats were randomly allocated to receive intraperitoneal cisplatin either alone or preceded by vitamins B, E or C or l-carnitine. Auditory brainstem response (i.e. hearing thresholds and wave I–IV intervals) and distortion product otoacoustic emissions (i.e. signal-to-noise ratios) were recorded before and 72 hours after cisplatin administration.

Results:

The following statistically significant differences were seen: control group pre- vs post-treatment wave I–IV interval values (p < 0.05); control vs vitamin E and B groups' I–IV interval values (p < 0.05); control vs other groups' hearing thresholds; vitamin E vs vitamin B and C and l-carnitine groups' hearing thresholds (p < 0.05); and vitamin B vs vitamin C and l-carnitine groups' hearing thresholds (p < 0.05). Statistically significant decreases were seen when comparing the initial and final signal-to-noise ratios in the control, vitamin B and l-carnitine groups (2000 and 3000 Hz; p < 0.01), and the initial and final signal-to-noise ratios in the control group (at 4000 Hz; p < 0.01).

Conclusion:

Vitamins B, E and C and l-carnitine appear to reduce cisplatin-induced ototoxicity in rats. The use of such additional treatments to decrease cisplatin-induced ototoxicity in humans is still under discussion.

Keywords

OtotoxicityCisplatinEar, InnerAntioxidantsRat

Information

Type
Main Articles
Information
The Journal of Laryngology & Otology , Volume 126 , Issue 5 , May 2012 , pp. 464 - 469
Copyright
Copyright © JLO (1984) Limited 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

1Jordan, J, Schwade, ND, Truelson, JM. Fosfomycin does not inhibit the tumoricidal efficacy of cisplatinum. Laryngoscope 1999;109:1259–62CrossRefGoogle Scholar
2Fram, RJ. Cisplatin and platinum analogues: recent advances. Curr Opin Oncol 1992;4:1073–9CrossRefGoogle ScholarPubMed
3Guneri, EA, Serbetçioglu, B, Ikiz, AO, Guneri, A, Ceryan, K. TEOAE monitoring of cisplatin induced ototoxicity in guinea pigs: the protective effect of vitamin B treatment. Auris Nasus Larynx 2001;28:9–14CrossRefGoogle ScholarPubMed
4Feghali, JG, Liu, W, Water, TRVD. L-N-acetyl-cysteine protection against cisplatin induced auditory neuronal and hair cell toxicity. Laryngoscope 2001;111:1147–55CrossRefGoogle ScholarPubMed
5Cardinaal, 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;144:135–46CrossRefGoogle ScholarPubMed
6Blakley, BW, Cohen, JI, Doolittle, ND, Muldoon, LL, Campbell, KC, Dickey, DT et al. Strategies for prevention of toxicity caused by platinum-based chemotherapy: review and summary of the annual meeting of the Blood–Brain Barrier Disruption Program, Gleneden Beach, Oregon, March 10, 2001. Laryngoscope 2002;112:1997–2001CrossRefGoogle Scholar
7Lynch, ED, Gu, R, Pierce, C, Kil, J. Reduction of acute cisplatin ototoxicity and nephrotoxicity in rats by oral administration of allopurinol and ebselen. Hear Res 2005;201:81–9CrossRefGoogle ScholarPubMed
8Rybak, LP, Whitworth, C, Somani, S. Application of antioxidants and other agents to prevent cisplatin ototoxicity. Laryngoscope 1999;109:1740–4CrossRefGoogle ScholarPubMed
9Ekborn, A, Anderssen, A, Ehrsson, H, Eksborg, S, Laurell, G, Wallin, I. Cisplatin-induced hearing loss: influence of the mode of drug administration in the guinea pig. Hear Res 2000;140:38–44CrossRefGoogle ScholarPubMed
10Schweitzer, VG. Cisplatin-induced ototoxicity: effect of pigmentation and inhibitory agents. Laryngoscope 1993;103:1–52Google ScholarPubMed
11Sakamoto, M, Kaga, K, Kamio, T. Extended high-frequency ototoxicity induced by the first administration of cisplatin. Otolaryngol Head Neck Surg 2000;122:828–33Google ScholarPubMed
12Reddel, RR, Kefford, RF, Grant, JM, Coats, AS, Fox, RM, Tattersall, MHN. Ototoxicity in patients receiving cisplatin: importance of dose and method of drug administration. Cancer Treat Rep 1982;66:19–23Google ScholarPubMed
13Rybak, LP, Husain, K, Evenson, L, Morris, C, Whitworth, C, Somani, SM. Protection by 4-methylthiobenzoic acid against cisplatin-induced ototoxicity: antioxidant system. Pharmacol Toxicol 1997;81:173–9CrossRefGoogle ScholarPubMed
14Saito, T, Aran, JM. Comparative ototoxicity of cisplatin during acute and chronic treatment. ORL J Otorhinolaryngol Relat Spec 1994;56:315–20CrossRefGoogle ScholarPubMed
15Giordano, P, Lorito, G, Ciorba, A, Martini, A, Hatzopoulos, S. Protection against cisplatin ototoxicity in a Sprague-Dawley rat animal model. Acta Otolaryngol Ital 2006;26:198–207Google Scholar
16Blumenreich, MS, Woodcock, TM, Richman, SP, Jones, MK, Gentile, PS, Kubota, TT et al. High dose cisplatin in patients with advanced malignancies. Cancer 1985;55:1118–223.0.CO;2-5>CrossRefGoogle ScholarPubMed
17Li, G, Frenz, DA, Brahmblatt, S, Feghali, JG, Ruben, RJ, Berggren, D et al. Round window membrane delivery of L-methionine provides protection from cisplatin ototoxicity without compromising chemotherapeutic efficacy. Neurotoxicology 2001;22:163–76CrossRefGoogle ScholarPubMed
18Ajith, TA, Usha, S, Nivitha, V. Ascorbic acid and alpha-tocopherol protect anticancer drug cisplatin induced nephrotoxicity in mice: a comparative study. Clin Chim Acta 2007;375:82–6CrossRefGoogle ScholarPubMed
19Ajith, TA, Abhishek, G, Roshny, D, Sudheesh, NP. Co-supplementation of single and multi doses of vitamins C and E ameliorates cisplatin-induced acute renal failure in mice. Exp Toxicol Pathol 2009;61:565–71CrossRefGoogle Scholar
20Wimmer, C, Mees, K, Stumpf, P, Welsch, U, Reichel, O, Suckfüll, M. Round window application of D-methionine, sodium thiosulfate, brain-derived neurotrophic factor, and fibroblast growth factor-2 in cisplatin-induced ototoxicity. Otol Neurotol 2004;25:33–40CrossRefGoogle ScholarPubMed
21Campbell, KCM, Larsen, DL, Meech, RP, Rybak, LP, Hughes, LF. Glutathione ester but not glutathione protects against cisplatin-induced ototoxicity in a rat model. J Am Acad Audiol 2003;14:124–33Google Scholar
22Hyppolito, MA, de Oliveira, JA, Rossato, M. Cisplatin ototoxicity and otoprotection with sodium salicylate. Eur Arch Otorhinolaryngol 2006;263:798–803CrossRefGoogle ScholarPubMed
23Kamimura, T, Whitworth, CA, Rybak, LP. Effect of 4-methylthiobenzoic acid on cisplatin-induced ototoxicity in the rat. Hear Res 1999;131:117–27CrossRefGoogle ScholarPubMed
24Dehne, N, Lautermann, J, Petrat, F, Rauen, U, de Groot, H. Cisplatin ototoxicity: involvement of iron and enhanced formation of superoxide anion radicals. Toxicol Appl Pharmacol 2001;174:27–34CrossRefGoogle ScholarPubMed
25Rybak, LP, Husain, K, Morris, C, Whitworth, C, Somani, S. Effect of protective agents against cisplatin ototoxicity. Am J Otol 2000;21:513–20Google ScholarPubMed
26Weijl, NI, Hopman, GD, Wipkink-Bakker, A, Lentjes, EG, Berger, HM, Cleton, FJ et al. Cisplatin combination chemotherapy induces a fall in plasma anti-oxidants of cancer patients. Ann Oncol 1998;9:1331–7CrossRefGoogle ScholarPubMed
27Teranishi, M, Nakashima, T, Wakabayashi, T. Effects of alpha-tocopherol on cisplatin-induced ototoxicity in guinea pigs. Hear Res 2001;151:61–70CrossRefGoogle ScholarPubMed
28Hatano, M, Uramoto, N, Okabe, Y, Furukawa, M, Ito, M. Vitamin E and vitamin C in the treatment of idiopathic sudden sensorineural hearing loss. Acta Otolaryngol 2008;128:116–21CrossRefGoogle ScholarPubMed
29Freitas, MR, Silva, VC, Brito, GA, Carvalho, JV Jr, Gomes, RM Jr , Ribeiro R de, A. Distortion-product otoacoustic emissions and auditory brainstem responses sensitivity assessment in cisplatin-induced ototoxicity in rats. Braz J Otorhinolaryngol 2009;75:476–84Google ScholarPubMed
30Shaw, NA. The auditory evoked potential in the rat – a review. Prog Neurobiol 1988;31:19–45CrossRefGoogle ScholarPubMed
31Kalkanis, JG, Whitworth, C, Rybak, LP. Vitamin E reduces cisplatin ototoxicity. Laryngoscope 2004;114:538–42CrossRefGoogle ScholarPubMed
32Leonetti, C, Biroccio, A, Gabellini, C, Scarsella, M, Maresca, V, Flori, E et al. Alpha-tocopherol protects against cisplatin-induced toxicity without interfering with antitumor efficacy. Int J Cancer 2003;104:243–50CrossRefGoogle ScholarPubMed
33Seidman, MD, Khan, MJ, Bai, U, Shirwany, N, Quirk, WS. Biologic activity of mitochondrial metabolites on aging and age-related hearing loss. Am J Otol 2000;21:161–7CrossRefGoogle ScholarPubMed
34Bielefeld, EC, Coling, D, Chen, GD, Henderson, D. Multiple dosing strategies with acetyl L-carnitine (ALCAR) fail to alter age-related hearing loss in the Fischer 344/NHsd rat. J Negat Results Biomed 2008;7:4CrossRefGoogle ScholarPubMed
35Coleman, JK, Kopke, RD, Liu, J, Ge, X, Harper, EA, Jones, GE et al. Pharmacological rescue of noise induced hearing loss using N-acetylcysteine and acetyl-L-carnitine. Hear Res 2007;226:104–13CrossRefGoogle ScholarPubMed