Auris Nasus Larynx 28 (2001) 9–14
TEOAE monitoring of Cisplatin induced ototoxicity in guinea
pigs: the protective effect of vitamin B treatment
Enis Alpin Gu ¨ neri *, Bu ¨lent S ¸ erbetc ¸iog ˘lu, Ahmet O mer I kiz, Ataman Gu ¨ neri,
Kerim Ceryan
Department of Otorhinolaryngolgy, Dokuz Eylu ¨l Uniersity Medical School, 3540, I nciraltı, I zmir, Turkey
Received 10 September 1999; received in revised form 18 November 1999; accepted 28 January 2000
Abstract
Objectie: To evaluate Cisplatin (CP) induced ototoxicity and the effects of vitamin B treatment on ototoxicity in guinea pigs
by using the Transient Evoked Otoacoustic Emission (TEOAE) technique. Methods: Eleven guinea pigs were divided into two
groups and they were tested by TEOAE before and after the experiment. A TEOAE response was regarded as positive when all
of the following criteria were met: 1. The mean amplitude of the cochlear response in dB pe SPL should be greater than that of
the noise in the external auditory canal; 2. The reproducibility rate of the response should be greater than 50%; 3. The stimulus
stability rate should be greater than 65%; 4. The signal to noise ratio of the response in 1, 2, 3, 4 and 5 kHz band frequencies
should be greater than 3 dB pe SPL in at least two bands. The first group included five animals that had only CP injections. Six
animals in the second group received additional 0.2 ml/kg combined vitamin B preparations for 7 consecutive days. Thereafter,
the right and left ears of all animals in both groups were tested by TEOAE. Results: TEOAE responses recorded from 22 ears
of 11 guinea pigs before drug administrations showed that the responses with maximum amplitude were originated from the
mid-frequency region. Positive TEOAE responses were significantly reduced after CP administrations in both groups when
compared with their respective pretreatment results (P 0.01). However, vitamin B injections, in addition to a single large dose
of CP, resulted in significantly better TEOAE responses than those obtained after only CP injections (P 0.05). Conclusions: The
routine use of TEOAE monitoring is recommended in clinical CP treatment protocols for the early detection and follow up of
ototoxicity. Also, prospective clinical trials are needed in order to validate the protective effects of vitamin B treatment against
ototoxicity. © 2001 Elsevier Science Ireland Ltd. All rights reserved.
Keywords: Guinea pigs; Otoacoustic emissions; Ototoxicity; Vitamin B
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1. Introduction
Cis-diammineedichloroplatinum (Cisplatin, CP) is a
chemotherapeutic agent frequently used for the treat-
ment of head and neck neoplasms whose side effects
include ototoxicity, nephrotoxicity, bone marrow su-
pression and gastrointestinal disturbances. The inci-
dence of ototoxicity due to CP treatment was reported
to vary between 4 and 50% [1–3]. Furthermore, high
frequency audiometry has shown that virtually all cases
treated with CP suffer from some sort of sensorineural
hearing loss [4].
CP ototoxicity was thought to result from increased
amounts of toxic free radicals [7–9] or cell membrane
changes leading to a decreased intracellular calcium
content [10 – 12]. The clinical picture includes a moder-
ate degree of high frequency sensorineural hearing loss
accompanied by tinnitus. The hearing loss is generally
bilateral, progressive and irreversible in nature; rarely
unilateral hearing losses and temporary threshold shifts
may be encountered [1,3].
Human and animal experiments have revealed that
the primary target affected by CP ototoxicity is the
outer hair cell (OHC) population located in the basal
and middle turns of the cochlea [1,4,13]. The loss of
OHC function leads to a disturbance in the mecha-
Presented as a poster at Otology 2000: Achievements and Per-
spectives, 15 – 19 August 1999, University of Zurich, Switzerland.
* Corresponding author. Present address: Mithatpas ¸a cad., 146/12
Karatas ¸ 35260, I zmir, Turkey. Tel.: +90-232-2777777/3251; fax:
+90-232-2590541.
E-mail address: alpin.guneri@deu.edu.tr (E.A. Gu ¨ neri).
0385-8146/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved.