The Laryngoscope
Lippincott Williams & Wilkins, Inc.
© 2004 The American Laryngological,
Rhinological and Otological Society, Inc.
Protective Effect of Corticosteroid against
the Cytotoxicity of Aminoglycoside Otic
Drops on Isolated Cochlear Outer Hair Cells
Seong Kook Park, MD; Dukjoo Choi, MD; Paul Russell, MD; Earnest O. John, PhD;
Timothy T. K. Jung, MD, PhD
Objectives: Otic drops are commonly used not
only for otitis externa but also for otorrhea in the
presence of tympanic membrane perforation or tym-
panostomy tube. Many studies demonstrated the oto-
toxicity of aminoglycoside. In our previous study, we
observed that gentamicin (GM), when activated with
liver extract, demonstrated significant cytotoxicity.
The purpose of this study was to assess the protective
effect of corticosteroid against the cytotoxicity of GM
and tobramycin drops using isolated cochlear outer
hair cells (OHCs) in vitro with liver extract. Methods:
OHCs from adult chinchilla cochleae were exposed to
standard bathing solution, liver extract alone, and
aminoglycoside otic drops with and without cortico-
steroid and liver extract. All experiments were per-
formed at an osmolality of 305 5 mOsm, at room
temperature, and for up to 60 minutes. The images of
OHCs were recorded using an inverted microscope
and analyzed on the Image Pro-Plus 3.0 program.
Time to cell death and change of cell length were
measured and analyzed. Results: The time to cell
death and percent change in cell length observed was
significantly longer in the GM liver extract dexa-
methasone group than the GM liver extract group
(P < .05). The Tobradex liver extract group showed
an insignificant increase in percent change of cell
length (P > .05) and significantly increased time to
cell death than the tobramycin liver extract group
(P < .05). Conclusion: This study demonstrated that
dexamethasone significantly reduced aminoglyco-
side cytotoxicity. Key Words: Aminoglycoside, ototox-
icity, corticosteroid, isolated cochlear outer hair cell.
Laryngoscope, 114:768 –771, 2004
INTRODUCTION
Topical otic drops are commonly used to treat otitis ex-
terna. It is used also for both acute and chronic otitis media in
the presence of otorrhea with tympanic membrane perforation
or tympanostomy tube. Cortisporin otic suspension (neomycin,
polymyxin B, and hydrocortisone) is the most widely used otic
drop in this country and has been used as a standard for
comparison of ototoxicity.
1
In addition, aminoglycoside ophthal-
mic preparations containing gentamicin (GM) or tobramycin
are commonly used for the treatment of otitis externa or otor-
rhea. When otic drops are topically applied in the presence of a
tympanic membrane perforation or tympanostomy tube, there
is a potential for the drug to enter into the inner ear by way of
the round window membrane. Isolated cochlear outer hair cells
(OHCs) were previously used to determine ototoxicity of com-
mon otic drops.
2,3
Ototoxicity of aminoglycoside antibiotics has been well
recognized. Exposure of the inner ear to a sufficient concen-
tration of aminoglycoside antibiotics, such as kanamycin,
GM, and neomycin, causes destruction of sensory hair cells,
resulting in permanent hearing loss (HL).
4,5
The mechanism
of GM ototoxicity is thought to proceed as follows: GM che-
lates iron, and the iron-GM complex catalyzes the production
of reactive oxygen species (ROS). The iron-GM complex pro-
duces free radicals that induce ototoxicity.
6
Studies over the
years have demonstrated the protective action of a variety of
agents against ototoxic effects. These agents include neural
growth factors,
7
N-ethyl-D-aspartate receptor antagonists,
8
scavengers of ROS,
9
iron chelators,
10
and dexamethasone.
11
The purpose of this study was to assess the protective effect
of corticosteroid against the ototoxicity of GM and tobramy-
cin drops using isolated cochlear OHCs in vitro.
MATERIALS AND METHODS
Isolation of OHCs, Preparation of Standard
Bathing Solution, and General Experimental
Protocol
Adult chinchillas weighing 400 to 600 g were anesthetized
by intramuscular ketamine (40 mg/kg) and xylazine (2 mg/kg).
After deep anesthesia was achieved, temporal bones and bony otic
From the Division of Otolaryngology–Head and Neck Surgery, Loma
Linda University School of Medicine, Loma Linda, California; and Jerry L.
Pettis Veterans Medical Center, Loma Linda, California, U.S.A.
This work was supported by the Division of Otolaryngology-Head
and Neck Surgery, Department of Surgery, Loma Linda University School
of Medicine and Jerry L. Pettis Memorial Veterans Administration Medical
Center, Loma Linda, California.
Editor’s Note: This Manuscript was accepted for publication Novem-
ber 8, 2003.
Send Correspondence to Dr. Timothy T. K. Jung, 11790 Pecan Way,
Loma Linda, CA 92354, U.S.A. E-mail: tjung1790@aol.com
Laryngoscope 114: April 2004 Park et al.: Protective Effect of Corticosteroid
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