TEOAE monitoring of Cisplatin induced ototoxicity in guinea pigs: the protective effect of vitamin B treatment

Abstract

Objective: 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.

Introduction

Cis-diammineedichloroplatinum (Cisplatin, CP) is a chemotherapeutic agent frequently used for the treatment of head and neck neoplasms whose side effects include ototoxicity, nephrotoxicity, bone marrow supression and gastrointestinal disturbances. The incidence of ototoxicity due to CP treatment was reported to vary between 4 and 50% [1], [2], [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], [8], [9] or cell membrane changes leading to a decreased intracellular calcium content [10], [11], [12]. The clinical picture includes a moderate 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 mechanoelectrical transduction of sound, thereby negatively affecting the sensitivity and frequency selectivity of the cochlea [14], [15].

Various agents were previously used clinically and experimentally in an effort to decrease or prevent CP induced ototoxicity. These include methylthiobenzoic acid [7], phosphomycine [16], thiosulphate [17], glutathion [18], retinoic acid [19] and pantothenic acid [10]. In this study, the effect of vitamin B complex treatment on CP induced ototoxicity in guinea pigs was evaluated by using transient evoked otoacoustic emissions (TEOAE).