Ototoxic effect of topical rifamycin SV applied in the middle ear of rats

Yıl 2017, Cilt: 27 Sayı: 1, 31 - 38, 05.03.2017

Can Özbay Mustafa Şahin

Öz

Objectives: In this study, we aimed to evaluate the ototoxic effect of topical rifamycin SV in the middle ear in a rat model. Materials and Methods: A total of 24 20-week-old adult female and eight 4-6-week-old weaned young, post-suckling period Wistar albino rats were used. Adult rats were separated into four groups: Group 1 adult rifamycin , group 2 weaner rifamycin , group 3 gentamicin; positive control , and group 4 saline; negative control . Before medication administration, an auditory brainstem response ABR test was performed on each animal under general anesthesia. Tympanic membranes of the animals were perforated, and the medications were administered to the middle ear for 10 days. Three weeks after treatment, ABR tests were repeated and pre- and posttreatment ABR threshold measurements were compared. Results: Although the mean pre- and post-treatment ABR threshold values did not significantly differ among groups 1, 2, and 4 p>0.05 , the mean post-treatment ABR threshold values were significantly higher in group 3 compared to baseline p<0.05 . Conclusion: Based on ABR measurements, the topical use of rifamycin SV, a broad-spectrum semi-synthetic antibiotic in the middle ear, does not cause hearing loss in adult or weaner rats.

Anahtar Kelimeler

Auditory brainstem response, inner ear, ototoxicity, rifamycin SV

Sıçan orta kulağına uygulanan topikal rifamisin SV’nin ototoksik etkisi

Öz

Amaç: Bu çalışmada bir sıçan modelinde topikal rifamisin SV’nin orta kulakta ototoksik etkisi araştırıldı.Gereç ve Yöntemler: Toplamda 24 adet, 20 haftalık erişkin dişi ve sekiz adet 4-6 haftalık sütten kesilmiş yavru Wistar albino sıçan kullanıldı. Erişkin sıçanlar dört gruba ayrıldı; Grup 1 erişkin rifamisin , grup 2 yavru rifamisin , grup 3 gentamisin; pozitif kontrol , grup 4 salin, negatif kontrol . İlaç uygulaması öncesinde her sıçana genel anestezi altında işitsel beyinsapı yanıtı ABR testi uygulandı. Hayvanların timpan membranları perfore edilerek, orta kulağa 10 gün boyunca ilaçlar uygulandı. Tedaviden üç hafta sonra ABR testleri tekrar edildi ve tedavi öncesi ve sonrası ABR eşik ölçümleri karşılaştırıldı.Bulgular: Tedavi öncesi ve tedavi sonrası ortalama ABR eşik değerleri grup 1, grup 2 ve grup 4’te istatistiksel olarak anlamlı farklılık göstermez iken p>0.05 , grup 3’te tedavi sonrası ortalama ABR eşik değerleri, başlangıca kıyasla, anlamlı düzeyde daha yüksekti p

Anahtar Kelimeler

İşitsel beyinsapı yanıtı, iç kulak, ototoksisite, rifamisin SV

Kaynakça

• Brummett RE, Morrison RB. The incidence of aminoglycoside antibiotic-induced hearing loss. Arch Otolaryngol Head Neck Surg 1990;116:406-10.
• Segal JA, Skolnick P. Polyamine-like actions of aminoglycosides and aminoglycoside derivatives at NMDA receptors. Eur J Pharmacol 1998;347:311-7.
• Masum S, Fakir M. Systemic antibiotics versus topical treatments for chronic discharging ears with underlying eardrum perforations. J Dhaka Med Col 2010;19:86-90.
• Dohar J. Eardrops for Otorrhoea. In: Alper CM, Bluestone CD, Dohar JE, Mandel EM. Casselbrant ML. Advanced Therapy of Otitis Media.1th ed..Ontaria: BC Decker Inc; 2004. p. 246-53.
• Rutka J. Topical aminoglycosides? No. The case against using these agents in chronic ear disease. Ear Nose Throat J 2003;82:9-12.
• Silverstein H, Hyman SM, Feldbaum J, Silverstein D. Use of streptomycin sulfate in the treatment of Meniere’s disease. Otolaryngol Head Neck Surg 1984;92:229-32.
• Nedzelski JM, Schessel DA, Bryce GE, Pfleiderer AG. Chemical labyrinthectomy: local application of gentamicin for the treatment of unilateral Menière’s disease. Am J Otol 1992;13:18-22.
• Pappas S, Nikolopoulos TP, Korres S, Papacharalampous G, Tzangarulakis A, Ferekidis E. Topical antibiotic ear drops: are they safe? Int J Clin Pract 2006;60:1115-9.
• Konno K, Oizumi K, Oka S. Mode of action of rifampin on mycobacteria. II. Biosynthetic studies on the inhibition of ribonucleic acid polymerase of Mycobacterium bovis BCG by rifampin and uptake of rifampin- 14 C by Mycobacterium phlei. Am Rev Respir Dis 1973;107:1006-12.
• Scarpignato C, Pelosini I. Rifaximin, a poorly absorbed antibiotic: pharmacology and clinical potential. Chemotherapy 2005;51:36-66.
• Sagit M, Somdas MA, Korkmaz F, Akcadag A. The ototoxic effect of intratympanic terbinafine applied in the middle ear of rats. J Otolaryngol Head Neck Surg 2013;42:13
• Oztürkcan S, Dündar R, Katilmis H, Ilknur AE, Aktaş S, Haciömeroğlu S. The ototoxic effect of boric acid solutions applied into the middle ear of guinea pigs. Eur Arch Otorhinolaryngol 2009;266:663-7.
• Pickett BP, Shinn JB, Smith MF. Ear drop ototoxicity: reality or myth? Am J Otol 1997;18:782-9.
• Tom LW. Ototoxicity of common topical antimycotic preparations. Laryngoscope 2000;110:509-16.
• Perez R, Freeman S, Sohmer H, Sichel JY. Vestibular and cochlear ototoxicity of topical antiseptics assessed by evoked potentials. Laryngoscope 2000;110:1522-7.
• Suzuki M, Kashio A, Sakamoto T, Yamasoba T. Effect of Burow's solution on the guinea pig inner ear. Ann Otol Rhinol Laryngol 2010;119:495-500.
• Ikeda K, Morizono T. The preparation of acetic acid for use in otic drops and its effect on endocochlear potential and pH in inner ear fluid. Am J Otolaryngol 1989;10:382-5.
• Chen JM, Kakigi A, Hirakawa H, Mount RJ, Harrison RV. Middle ear instillation of gentamicin and streptomycin in chinchillas: morphologic appraisal of selective ototoxicity. J Otolaryngol 1999;28:121-8.
• Patterson WC, Gulick WL. The effects of chloramphenicol upon the electrical activity of the ear. Ann Otol Rhinol Laryngol 1963;72:50-5.
• Halama AR, Wright CG, Meyerhoff WL. Ototoxicity of an ototopic preparation--experimental results and clinical facts. Acta Otorhinolaryngol Belg 1991;45:279-82.
• Rutherford KD, Kavanagh K, Parham K. Auditory function after application of ototopical vancomycin and mupirocin solutions in a murine model. Otolaryngol Head Neck Surg 2011;144:419-26.
• Oshima H, Nomura K, Yamazaki M, Suzuki J, Kawase T, Kobayashi T, et al. Ototoxic effect of daptomycin applied to the guinea pig middle ear. Acta Otolaryngol 2014;134:679-83.
• Bagger-Sjöbäck D, Lundman L, Nilsson-Ehle I. Ciprofloxacin and the inner ear--a morphological and round window membrane permeability study. ORL J Otorhinolaryngol Relat Spec 1992;54:5-9.
• Gates GA. Safety of ofloxacin otic and other ototopical treatments in animal models and in humans. Pediatr Infect Dis J 2001;20:104-7.
• Brown OE, Wright CG, Masaki M, Meyerhoff WL. Ototoxicity of Vasocidin drops applied to the chinchilla middle ear. Arch Otolaryngol Head Neck Surg 1988;114:56-9.
• Sisti F, Vaccaro L. Local application of rifamycin SV in caverns treated by endocavitary aspiration. Arch Tisiol Mal Appar Respir 1963;18:251-6. [Abstract]
• Kaya A, Kaya B, Aktas A, Firat ET. Effect of rifampin in combination with allogeneic, alloplastic, and heterogenous bone grafts on bone regeneration in rat tibial bone defects. Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 2015;27:20-8.
• Iselin F, Audren JL, Gouet O, Hautefort E, Peze W, Pradet G. Comparative study of the effects of a local antibiotic and a local antiseptic in emergency hand surgery. Ann Chir Main Memb Super 1990;9:65-71. [Abstract]
• Köşüş A, Köşüş N, Güler A, Çapar M. Rifamycin sv application to subcutaneous tissue for prevention of post-cesarean surgical site infection. Eur J Gen Med 2010;7:269-76.
• Caruso I, Montrone F, Fumagalli M, Patrono C, Santandrea S, Gandini MC. Rheumatoid knee synovitis successfully treated with intra-articular rifamycin SV. Ann Rheum Dis 1982;41:232-6.
• Prantera C, Lochs H, Grimaldi M, Danese S, Scribano ML, Gionchetti P. Rifaximin-extended intestinal release induces remission in patients with moderately active Crohn's disease. Gastroenterology 2012;142:473-81.
• Gionchetti P, Rizzello F, Ferrieri A, Venturi A, Brignola C, Ferretti M, et al. Rifaximin in patients with moderate or severe ulcerative colitis refractory to steroid-treatment: a double-blind, placebo-controlled trial. Dig Dis Sci 1999;44:1220-1.
• Mencarelli A, Migliorati M, Barbanti M, Cipriani S, Palladino G, Distrutti E, et al. Pregnane-X-receptor mediates the anti-inflammatory activities of rifaximin on detoxification pathways in intestinal epithelial cells. Biochem Pharmacol 2010;80:1700-7.
• Cheng J, Shah YM, Ma X, Pang X, Tanaka T, Kodama T. Therapeutic role of rifaximin in inflammatory bowel disease: clinical implication of human pregnane X receptor activation. J Pharmacol Exp Ther 2010;335:32-41.
• Magnan A, Venemalm L, Porri F, Vervloet D. Anaphylactic reaction to rifamycin SV: presence of specific IgE antibodies. J Allergy Clin Immunol 1999;103:954-6.
• Ebo DG, Verheecke G, Bridts CH, Mertens CH, Stevens WJ. Perioperative anaphylaxis from locally applied rifamycin SV and latex. Br J Anaesth 2006;96:738-41.
• Juhn SK, Hamaguchi Y, Goycoolea M. Review of round window membrane permeability. Acta Otolaryngol Suppl 1989;457:43-8.
• Becvarovski Z, Bojrab DI, Michaelides EM, Kartush JM, Zappia JJ, LaRouere MJ. Round window gentamicin absorption: an in vivo human model. Laryngoscope 2002;112:1610-3.
• Rifamycin SV Sodium Salt. National Center for Biotechnology Information. PubChem Compound Database; CID=46174110. Available from: https:// pubchem.ncbi.nlm.nih.gov/compound/46174110 (Accessed: March 13, 2017).