N-chlorotaurine, a novel endogenous antimicrobial agent: tolerability testing in a mouse model.
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 microL 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.


CONCLUSIONS
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.
Neher
A
A
Department of Otorhinolaryngology, University of Innsbruck, Anichstr 35, A-6020 Innsbruck, Austria. Andreas.Neher@uibk.ac.at
Nagl
M
M
Schrott-Fischer
A
A
Ichiki
H
H
Gottardi
W
W
Gunkel
A R
AR
Stephan
K
K
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004361:Drug Tolerance; D007758:Ear, Inner / Q000187:drug effects; D004432:Ear, Middle; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005839:Gentamicins / Q000008:administration & dosage / Q000494:pharmacology; D007267:Injections; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology; D013654:Taurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014298:Trimethyltin Compounds / Q000008:administration & dosage / Q000494:pharmacology
D000890:Anti-Infective Agents; D005839:Gentamicins; D014298:Trimethyltin Compounds; C046488:trimethyltin; D013654:Taurine; D012965:Sodium Chloride; C043410:N-chlorotaurine