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N-Chlorotaurine, a Novel Endogenous Antimicrobial Agent
Tolerability Testing in a Mouse Model
Andreas Neher, MD;
Markus Nagl, MD;
Anneliese Schrott-Fischer, PhD;
Hiroto Ichiki, MD;
Waldemar Gottardi, PhD;
Andreas R. Gunkel, MD;
Kurt Stephan, PhD
Arch Otolaryngol Head Neck Surg. 2001;127:530-533.
Objective To investigate the tolerability of N-chlorotaurine,
a new antimicrobial agent, by application to the middle ear in a mouse model.
Methods Five BALB/c mice were each injected through the tympanic membrane with
5 µL of 0.1%, 1.0%, and 10% N-chlorotaurine
and compared with animals in which 0.9% isotonic sodium chloride solution,
0.2% gentamicin sulfate, and 0.25% trimethyltin chloride were instilled. Auditory
brainstem responses to clicks were evaluated repeatedly between 4 and 75 days
after injection, and histologic investigations of the inner ear were performed
subsequently. Three additional groups of mice were injected with isotonic
sodium chloride solution, 1.0% N-chlorotaurine, and
0.25% trimethyltin, and brainstem responses to tone bursts of 8, 16, and 32
kHz were tested. In addition, the middle ear was examined histologically.
Results Mice treated with isotonic sodium chloride solution, 0.1% N-chlorotaurine, and 0.2% gentamicin sulfate did not show changes in
response threshold. Treatment with 1.0% and 10% N-chlorotaurine
caused a reversible increase in auditory brainstem response threshold by 20
dB 4 days after application because of local irritation around the perforation
of the tympanic membrane. In contrast, 0.25% trimethyltin showed a permanent
elevation of auditory brainstem response threshold of 10 to 15 dB and a scattered
loss of outer hair cells predominantly in the apical turn. No alterations
of the inner ear were observed in the other treatment groups. The mucous membrane
of the middle ear remained unaffected in all test groups.
Conclusion Application of N-chlorotaurine to the middle
ear is well tolerated without adverse effects and may be a useful new endogenous
antimicrobial agent for local treatment of otologic infections.
From the Department of Otorhinolaryngology (Drs Neher and Gunkel),
Institute of Hygiene and Social Medicine (Drs Nagl and Gottardi), Inner Ear
Research Laboratory, Department of Otorhinolaryngology (Drs Schrott-Fischer
and Ichiki), and Department for Hearing, Speech, and Voice Disorders (Dr Stephan),
Leopold-Franzens-University, Innsbruck, Austria; and Department of Otolaryngology,
Self-Defense Forces Central Hospital, Tokyo, Japan (Dr Ichiki).
Corresponding author and reprints: Andreas Neher, MD, Department
of Otorhinolaryngology, University of Innsbruck, Anichstr 35, A-6020 Innsbruck,
Austria (e-mail: Andreas.Neher{at}uibk.ac.at).
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