Hostname: page-component-586b7cd67f-2plfb Total loading time: 0 Render date: 2024-11-22T15:56:42.688Z Has data issue: false hasContentIssue false
  • English
  • Français

Local and systemic effects of low-dose transtympanic methotrexate: in vivo animal study

Published online by Cambridge University Press:  10 December 2012

E Sozen ,
S B Erol ,
O Yildirim ,
B U Coskun ,
T Basak ,
F T Kayhan  and
B Dadas
E Sozen*
Affiliation:
Department of Otorhinolaryngology (Clinic II), Sisli Etfal Training and Research Hospital, Istanbul, Turkey
S B Erol
Affiliation:
Department of Otorhinolaryngology (Clinic II), Sisli Etfal Training and Research Hospital, Istanbul, Turkey
O Yildirim
Affiliation:
Department of Otorhinolaryngology (Clinic II), Sisli Etfal Training and Research Hospital, Istanbul, Turkey
B U Coskun
Affiliation:
Department of Otorhinolaryngology (Clinic II), Sisli Etfal Training and Research Hospital, Istanbul, Turkey
T Basak
Affiliation:
Department of Pathology, Sisli Etfal Training and Research Hospital, Istanbul, Turkey
F T Kayhan
Affiliation:
Department of Otorhinolaryngology, Bakırkoy Dr Sadi Konuk Training and Research Hospital, Istanbul, Turkey
B Dadas
Affiliation:
Department of Otorhinolaryngology (Clinic II), Sisli Etfal Training and Research Hospital, Istanbul, Turkey
*
Address for correspondence: Dr Esra Sozen, Department of Otorhinolaryngology, Clinic II, Sisli Etfal Training and Research Hospital, Istanbul, Turkey Fax: +90 2122962264 E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective:

To evaluate the safety of low-dose transtympanic methotrexate in a rat model.

Design:

Experimental animal study.

Setting:

Tertiary training and research hospital.

Methods:

Twenty-four rats were randomly divided into three study groups. Diluted methotrexate solution was administered transtympanically to fill the middle-ear cavity, twice a week in group one and three times a week in group two. Ringer lactate solution was administered transtympanically three times a week in the control group.

Main outcome measures: Local and systemic effects of low-dose transtympanic methotrexate.

Results:

In the methotrexate groups, middle-ear mucosal oedema was present in all animals. Auditory brainstem response thresholds indicated no inner-ear dysfunction in any group. Liver function and serum haemoglobin levels showed no statistically significant difference in any group. However, liver biopsies from groups one and two showed mild portal hyperaemia.

Conclusion:

These findings are encouraging, and support further investigation of the topical application of methotrexate in autoimmune hearing diseases, as an alternative or adjunct to transtympanic steroids.

Keywords

MethotrexateEar, MiddleEar, InnerAutoimmunityDrug Administration Routes
Type
Main Articles
Information
The Journal of Laryngology & Otology , Volume 127 , Issue 2 , February 2013 , pp. 148 - 152
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.)

References

1McCabe, BF. Autoimmune sensorineural hearing loss. Ann Otol Rhinol Laryngol 1979;113:526–30CrossRefGoogle Scholar
2ten Cate, WJ, Bachor, E. Autoimmune-mediated sympathetic hearing loss: a case report. Otol Neurotol 2005;26:161–5CrossRefGoogle ScholarPubMed
3Ryan, AF, Keithley, EM, Harris, JP. Autoimmune inner ear disorders. Curr Opin Neurol 2001;14:35–40CrossRefGoogle ScholarPubMed
4Sismanis, A, Wise, CM, Johnson, GD. Methotrexate management of immune-mediated cochleovestibular disorders. Otolaryngol Head Neck Surg 1997;116:146–52Google ScholarPubMed
5Salley, LH Jr, Grimm, M, Sismanis, A, Spencer, RF, Wise, CM. Methotrexate in the management of immune mediated cochleovestibular disorders: clinical experience with 53 patients. J Rheumatol 2001;28:1037–40Google ScholarPubMed
6Matteson, EL, Fabry, DA, Facer, GW, Beatty, CW, Driscoll, CL, Strome, SE et al. Open trial of methotrexate as treatment for autoimmune hearing loss. Arthritis Rheum 2001;45:146–503.0.CO;2-I>CrossRefGoogle ScholarPubMed
7Matteson, EL, Tirzaman, O, Facer, GW, Fabry, DA, Kasperbauer, J, Beatty, CW et al. Use of methotrexate for autoimmune hearing loss. Ann Otol Rhinol Laryngol 2000;109:710–14CrossRefGoogle ScholarPubMed
8Cohen, S, Shoup, A, Weisman, MH, Harris, J. Etanercept treatment for autoimmune inner ear disease: results of a pilot placebo-controlled study. Otol Neurotol 2005;26:903–7CrossRefGoogle ScholarPubMed
9Matteson, EL, Choi, HK, Poe, DS, Wise, C, Lowe, VJ, McDonald, TJ et al. Etanercept therapy for immune-mediated cochleovestibular disorders: a multi-center, open-label, pilot study. Arthritis Rheum 2005;53:337–42CrossRefGoogle ScholarPubMed
10Weinblatt, ME, Coblyn, JS, Fox, DA, Fraser, PA, Holdsworth, DE, Glass, DN et al. Efficacy of low dose methotrexate in rheumatoid arthritis. N Engl J Med 1985;312:818–22CrossRefGoogle ScholarPubMed
11Iagnocco, A, Cerioni, A, Coari, G, Ossandon, A, Masciangelo, R, Valesini, G. Intra-articular methotrexate in the treatment of rheumatoid arthritis and psoriatic arthritis: a clinical and sonographic study. Clin Rheumatol 2006;25:159–63CrossRefGoogle ScholarPubMed
12Ali, MF, Salah, M, Rafea, M, Saleh, N. Liposomal methotrexate hydrogel for treatment of localized psoriasis: preparation, characterization and laser targeting. Med Sci Monit 2008;14:166–74Google ScholarPubMed
13Ercan, I, Cakir, BO, Başak, T, Ozbal, EA, Sahin, A, Balci, G et al. Effects of topical application of methotrexate on nasal mucosa in rats: a preclinical assessment study. Otolaryngol Head Neck Surg 2006;134:751–5CrossRefGoogle ScholarPubMed
14Papadimitraki, ED, Kyrmizakis, DE, Kritikos, I, Boumpas, DT. Ear-nose-throat manifestations of autoimmune diseases. Clin Exp Rheumatol 2004;22:485–94Google Scholar
15Sismanis, A, Thompson, T, Willis, HE. Methotrexate therapy for autoimmune hearing loss: a preliminary report. Laryngoscope 1994;104:932–4CrossRefGoogle ScholarPubMed
16Harris, JP, Weisman, MH, Derebery, JM, Espeland, MA, Gantz, BJ, Gulya, AJ et al. Treatment of corticosteroid-responsive autoimmune inner ear disease with methotrexate: a randomized controlled trial. JAMA 2003;290:1875–83CrossRefGoogle ScholarPubMed
17Parnes, LS, Sun, AH, Freeman, DJ. Corticosteroid pharmacokinetics in the inner ear fluids: an animal study followed by clinical application. Laryngoscope 1999;109:1–17CrossRefGoogle ScholarPubMed
18Yang, GS, Song, HT, Keithley, EM, Harris, JP. Intratympanic immunosuppressives for prevention of immune-mediated sensorineural hearing loss. Am J Otol 2000;21:499–504Google ScholarPubMed
19Street, I, Jobanputra, P, Proops, DW. Etanercept, a tumour necrosis factor alpha receptor antagonist, and methotrexate in acute sensorineural hearing loss. J Laryngol Otol 2006;120:1064–6CrossRefGoogle ScholarPubMed
20Van Wijk, F, Staecker, H, Keithley, E, Lefebvre, PP. Local perfusion of the tumor necrosis factor alpha blocker infliximab to the inner ear improves autoimmune neurosensory hearing loss. Audiol Neurootol 2006;11:357–65CrossRefGoogle Scholar
21Silverstein, H, Arruda, J, Rosenberg, SI, Deems, D, Hester, TO. Direct round window membrane application of gentamicin in the treatment of Meniere's disease. Otolaryngol Head Neck Surg 1999;120:649–55CrossRefGoogle ScholarPubMed