Hostname: page-component-586b7cd67f-gb8f7 Total loading time: 0 Render date: 2024-11-23T23:49:25.011Z Has data issue: false hasContentIssue false

Light microscopy study of cisplatin-induced ototoxicity in rats

Published online by Cambridge University Press:  15 January 2009

M R de Freitas*
Affiliation:
Department of Surgery, Medical School, Federal University of Ceará, Fortaleza, Ceará, Brazil
G A de Castro Brito
Affiliation:
Department of Morphology, Medical School, Federal University of Ceará, Fortaleza, Ceará, Brazil
J V de Carvalho Jnr
Affiliation:
Department of Surgery, Medical School, Federal University of Ceará, Fortaleza, Ceará, Brazil
R M Gomes Jnr
Affiliation:
Department of Surgery, Medical School, Federal University of Ceará, Fortaleza, Ceará, Brazil
M J Barreto Martins
Affiliation:
Department of Surgery, Medical School, Federal University of Ceará, Fortaleza, Ceará, Brazil
R de Albuquerque Ribeiro
Affiliation:
Department of Physiology and Pharmacology, Medical School, Federal University of Ceará, Fortaleza, Ceará, Brazil
*
Address for correspondence: Dr Marcos Rabelo de Freitas, Department of Surgery, Medical School, Federal University of Ceará, Rua Professor Costa Mendes 1608, Rodolfo Teófilo, Fortaleza, Ceará, Brazil, CEP 60416-160 Fax: +55 85 3366 8064 E-mail: [email protected]

Abstract

Background:

Although most studies on animal ototoxicity employ scanning electron microscopy, all cochlear structures may be identified with light microscopy. This paper describes a simple method of histological assessment of cisplatin-induced ototoxicity in rats, and relates morphological changes to functional changes in hearing detected by distortion product evoked otoacoustic emissions.

Materials and methods:

Male Wistar rats were injected with 8 mg/kg/day cisplatin, or with an equivalent volume of saline solution, for three consecutive days. They underwent distortion product evoked otoacoustic emission testing at baseline and at 24 or 48 hours after the last administration. At the end of the experiment, the animals were sacrificed and their cochleae were retrieved and prepared for haematoxylin and eosin staining.

Results:

A four-point scoring system was used to grade injury to the external ciliated cells, as indicated by the number of cells absent from the basal turn of the cochlear duct. A four-point scoring system was also used to grade stria vascularis injury, as indicated by the degree of shrinkage of the intermediate cells. Scores were significantly higher in groups treated with cisplatin compared with controls. Morphological changes were confirmed by decreased distortion product evoked otoacoustic emission amplitudes in animals treated with cisplatin.

Conclusion:

This method is simple to perform with routine histology equipment and is appropriate for the study of acute, cisplatin-induced ototoxicity in rats.

Type
Main Articles
Copyright
Copyright © JLO (1984) Limited 2009

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.)

Footnotes

Presented at the 39th Brazilian Congress of Otorhinolaryngology, 2 March 2008, Brasília, DF, Brazil.

References

1 Oliveira, JAA, Canedo, DM, Rossato, M. Otoprotection of auditory hair cells against amikacin ototoxicity. Rev Bras Otorrinolaringol 2002;68:713Google Scholar
2 Jordan, JA, Schwade, ND, Truelson, JM. Fosfomycin does not inhibit the tumoricidal efficacy of cisplatinum. Laryngoscope 1999;109:1259–62Google Scholar
3 Güneri, EA, Serbetçiogllu, B, Ikiz, AO, Güneri, A, Ceryan, K. TEOAE monitoring of cisplatin induced ototoxicity in guinea pigs: the protective effect of vitamin B treatment. Auris Nasus Larynx 2001;28:914CrossRefGoogle ScholarPubMed
4 Feghali, 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
5 Campbell, KCM, Rybac, LP, Meech, RP. D-Methionine provides excellent protection from cisplatin ototoxicity in the rat. Hear Res 1996;102:90–8Google Scholar
6 Kamimura, T, Whitworth, CA, Rybak, LP. Effect of 4-methylthiobenzoic acid on cisplatin-induced ototoxicity in the rat. Hear Res 1999;131:117–27Google Scholar
7 Li, 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;22:163–76Google Scholar
8 Tanaka, F, Whitworth, CA, Rybak, LP. Round window pH manipulation alters the ototoxicity of systemic cisplatin. Hear Res 2004;187:4450CrossRefGoogle ScholarPubMed
9 Kalkanis, JK, Whitworth, MA, Rybak, LP. Vitamin E reduces cisplatin ototoxicity. Laryngoscope 2004;114:538–42CrossRefGoogle ScholarPubMed
10 Fetoni, AR, Quaranta, N, Marchese, R, Cadoni, G, Paludetti, G, Sergi, B. The protective role of tiopronin in cisplatin ototoxicity in Wistar rats. Int J Audiol 2004;43:465–70CrossRefGoogle ScholarPubMed
11 Campbell, KCM, Meech, RP, Rybak, LP, Hughes, LF. D-Methionine protects against cisplatin damage to the stria vascularis. Hear Res 1999;138:1328Google Scholar
12 Laurell, G, Viberg, A, Teixeira, M, Sterkers, O, Ferrary, E. Blood-perilymph barrier and ototoxicity: an in vivo study in rat. Acta Otolaryngol 2000;120:796803Google Scholar
13 De Groot, JCMJ, Hamers, FPT, Gispen, WH, Smoorenburg, GF. Co-administration of the neurotrophic ACTH(4-9) analogue, ORG 2766, may reduce the cochleotoxic effects of cisplatin. Hear Res 1997;106:919Google Scholar
14 Heijmen, PS, Klis, SFL, De Groot, JCMJ, Smoorenburg, GF. Cisplatin ototoxicity and the possibily protective effect of α-melanocyte stimulating hormone. Hear Res 1999;128:2739CrossRefGoogle Scholar
15 Cardinaal, 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;144:135–46Google Scholar
16 Cardinaal, RM, De Groot, JCMJ, Huizing, EH, Veldman, JE, Smoorenburg, GF. Cisplatin-induced ototoxicity: morphological evidence of spontaneous outer hair cell recovery in albino guinea pig? Hear Res 2000;144:147–56Google Scholar
17 Cardinaal, RM, De Groot, JCMJ, Huizing, EH, Veldman, JE, Smoorenburg, GF. Histological effects of co-administration of an ACTH4-9 analogue, ORG 2766, on cisplatin ototoxicity in the albino guinea pig. Hear Res 2000;144:157–67Google Scholar
18 Sergi, B, Ferraresi, A, Troiani, D, Paludetti, G, Fetoni, AR. Cisplatin ototoxicity in the guinea pig: vestibular and cochlear damage. Hear Res 2003;182:5664Google Scholar
19 Lynch, 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
20 Wang, RV, Faulconbridge, RVL, Fetoni, A, Guitton, MJ, Pujol, R, Puel, JL. Local application of sodium thiosulfate prevents cisplatin-induced hearing loss in the guinea pig. Neuropharmacology 2003;45:380–93CrossRefGoogle ScholarPubMed
21 Smoorenburg, GF, De Groot, JCMJ, Hamers, FPT, Klis, SFL. Protection and spontaneous recovery from cisplatin-induced hearing loss. Ann N Y Acad Sci 1999;28:192210CrossRefGoogle Scholar
22 O'Leary, SJ, Klis, SFL, De Groot, JCMJ, Hamers, FPT, Smoorenburg, GF. Perilymphatic application of cisplatin over several days in albino guinea pigs: dose dependency of electrophysiological and morphological effects. Hear Res 2001;154:135–45Google Scholar
23 Sluyter, S, Klis, SFL, De Groot, JCMJ, Smoorenburg, GF. Alterations in the stria vascularis in relation to cisplatin ototoxicity and recovery. Hear Res 2003;185:4956Google Scholar
24 Wolters, FLC, Klis, SFL, Hamers, FPT, De Groot, JCMJ, Smoorenburg, GF. Perilymphatic application of α-melanocyte stimulating hormone ameliorates hearing loss caused by systemic administration of cisplatin. Hear Res 2004;189:3140CrossRefGoogle ScholarPubMed
25 Van Ruijven, MWM, De Groot, JCMJ, Smoorenburg, GF. Time sequence of degeneration pattern in the guinea pig cochlea during cisplatin administration. A quantitative histological study. Hear Res 2004;197:4454CrossRefGoogle ScholarPubMed
26 Van Ruijven, MWM, De Groot, JCMJ, Klis, SFL, Smoorenburg, GF. The cochlear targets of cisplatin: an electrophysiological and morphological time-sequence study. Hear Res 2005;205:241–8CrossRefGoogle ScholarPubMed