Electrophysiological Study of the Effect of Sodium Salicylate Upon the Cochlea

Mitchell, Curt; Brummett, Robert E.; Himes, Donna; Vernon, Jack

doi:10.1001/archotol.1973.00780020309003

Cited by 39 publications

(14 citation statements)

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“…Second, other observations from our laboratory showed that salicylate increased 2-DG metabolic activity not only within inferior colliculus but in the cochlear nuclei complex as well (Kauer et al, 1982). Third, known pharmacological effects of salicylate, in doses analogous to ours, primarily affect the cochlea (Flower et al, 1980;McFadden and Plattsmier, 1983;McCabe and Dey, 1965;McPherson and Miller, 1974;Mitchell et al, 1973), whereas at such doses the effect of salicylate on the CNS has not been reported. Thus we postulate that the observed increase of spontaneous activity in IC originates in the cochlea.…”

Section: Discussionmentioning

confidence: 46%

“…It has been reported that cAMP is responsible for activation of sodium-potassium-ATPase and calciummagnesium-ATPase in some cell systems (Thaimann et al, 1982); thus it is possible to expect disturbances in ionic equilibrium within hair cells as has been directly observed in red blood cells (Burgin and Schatzmann, 1979 Dallos, 1981), it is possible to expect changes in the micromechanical properties of the cochlea, resulting in tinnitus (Tonndorf, 1980(Tonndorf, , 1981. Mitchell et al (1973) showed that although the concentration of salicylate in the blood rises rapidly after injection of sodium salicylate, the effects on auditory nerve action potential lag behind by 2-4 h. The elimination of salicylate can be described by Michealis-Menton paralleled with first-order elimination procedure with relative elimination rate decreasing with increasing dose (Levy, 1979). The plasma half-life for salicylate administered in high doses, as in the case with our experiments, equaled 15-30 h as contrasted with 2-3 h in low doses (Gold and Wilpizeski, 1966;Levy, 1979), due in part to the limited formation of salicylurate and salicyl phenolic glucuronide, which determines salicylate elimination (Levy et al, 1972).…”

Section: Discussionmentioning

confidence: 96%

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Salicylate-induced changes in spontaneous activity of single units in the inferior colliculus of the guinea pig

Jastreboff

Sasaki

1986

The Journal of the Acoustical Society of America

154

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Changes in spontaneous neuronal activity of the inferior colliculus in albino guinea pigs before and after administration of sodium salicylate were analyzed. Animals were anesthetized with pentobarbital, and two microelectrodes separated by a few hundred microns were driven through the inferior colliculus. After collecting a sufficiently large sample of cells, sodium salicylate (450 mg/kg) was injected i.p. and recordings again made 2 h after the injection. Comparison of spontaneous activity recorded before and after salicylate administration revealed highly statistically significant differences (p less than 0.001). After salicylate, the mean rate of the cell population increased from 29 to 83 Hz and the median from 26 to 74 Hz. Control experiments in which sodium salicylate was replaced by saline injection revealed no statistically significant differences in cell discharges. Recordings made during the same experiments from lobulus V of the cerebellar vermis revealed no changes in response to salicylate. The observed changes in single-unit activity due to salicylate administration may represent the first systematic evidence of a tinnituslike phenomenon in animals.

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Section: Discussionmentioning

confidence: 46%

Section: Discussionmentioning

confidence: 96%

Salicylate-induced changes in spontaneous activity of single units in the inferior colliculus of the guinea pig

Jastreboff

Sasaki

1986

The Journal of the Acoustical Society of America

154

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“…There have been numerous investigations of the electrical activity in the cochlea or auditory nerve on a salicylate effect, e.g., cochlear microphonic (CM) [4,13,24,27,28,30], summating potential (SP) and endocochlear potential (EP) [27,30], compound action potential (CAP) of the auditory nerve [27,30,31] and suppression of active cochlear processes [21]. Recent results suggest that the effects of salicylate may arise from alterations in the membrane capacitance of the OHC and consequent inhibition of OHC motility [32].…”

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confidence: 99%

A Characteristic of Aspirin-Induced Hearing Loss in Auditory Brainstem Response of Conscious Rats.

Kurata

Yamamoto

Tsukuda

et al. 1997

The Journal of Veterinary Medical Science

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ABSTRACT. The acute effects of aspirin on auditory functions were examined electrophysiologically in conscious rats with chronically implanted electrodes for auditory brainstem response (ABR) recording. A single intravenous injection of aspirin at a dose of 225 mg/kg caused a reduction in the amplitude of the ABR P1 wave evoked by a 2 kHz tone pip 1 and 24 hr after dosing at almost all sound intensity levels, while the P1 amplitude at 4 kHz was reduced mainly 1 hr after dosing, and the P1 amplitude at 8 kHz was not significantly affected at middle and high intensities even 1 hr after dosing. The audiogram obtained from the P1 amplitude showed a significant increase in the sound threshold 1 and 24 hr after dosing at 2 kHz, and 1 hr after dosing at 4 kHz, but not at 8 kHz. The peak latency of the P1 wave was also prolonged. Furthermore, reduction of the P2 and P4 wave amplitude and prolongation of the P1-P2 and P2-P4 interpeak latency were also observed at 2 kHz but not at 4 or 8 kHz. These results suggest that the rat auditory function for low frequency is vulnerable to the effects of aspirin. This paradigm, i.e., frequency selectivity, in rats may be useful to further assess the different outer hair cells along the cochlear duct and provide additional evidence for the mechanism(s) or site underlying aspirin ototoxicity. -KEY WORDS: ABR, aspirin, conscious rat, frequency selectivity.J. Vet. Med. Sci. 59(1): 9-15, 1997The mammalian cochlea performs a frequency analysis of airborne sound by processing different frequencies at different portions along the cochlear duct: high frequencies at the base and low frequencies at the apex. It has been reported that the hearing impairment induced by aspirin and salicylates in humans does not depend on the sound frequency [25], but others have claimed that higher frequencies are more susceptible to the effects of these drugs in humans and/or guinea pigs [8,10,22]. Boettcher and Salvi have reported that the results of the effects of aspirin on frequency selectivity are conflicting [3]. Most reports do agree that hearing loss and/or tinnitus are caused by these drugs. In almost all studies, the ototoxicity of aspirin and/or salicylate has been assessed in guinea pigs [8,11,27], monkeys [25,29] or cats [13,14,30], and little information is available on the effects of aspirin on the auditory function of rats. Recently it was indicated in rats that salicylate had a stronger effect on the otoacoustic emission distortion product for high and low frequencies with a clearly smaller effect for frequencies from the range of 6 to 8 kHz, and additionally, the loudness of salicylateinduced rat tinnitus was detected at moderate intensities corresponding to 62 dB SPL below 10 kHz by the behavioral response [18].If aspirin has a different effect at different OHCs along the cochlear duct in rats, aspirin's effect on the frequency selectivity may provide an additional approach to locating the mechanism or site of aspirin's action within the cochlea. In the present study, we examined the effects ...

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“…In addition, there are numerous studies of the electrical activity in the cochlea and auditory nerve on a salicylate effect, e.g., cochlear microphonic (CM) [1,3,8,14,25,28,29,31], summating potential (SP) [28,31], compound action potential (CAP) of the auditory nerve [28,31,32] and the endocochlear potential (EP) [28,31]. Nevertheless the impairment site (s) and mechanism (s) of aspirin and/or salicylate action from these results have not been resolved.…”

Section: Animals and Housing Conditionsmentioning

confidence: 99%

“…An origin of cochlear microphonic (CM) is the electrical activity of the cochlear OHCs with a contribution from the IHCs [28]. It is reported that the CM response in guinea pigs is uninfluenced by aspirin [14,25] and aspirin and/or salicylates reduced CM potential in guinea pigs [3,28,29]. Also, a slight increase in the CM response was observed following salicylate administration in cats [31].…”

Section: 2mentioning

confidence: 99%

Frequency Selectivity on Aspirin-Induced Hearing Loss in Rats with Auditory Stimulus-Induced Conditioned Suppression.

Kurata

Nishida

Tsukuda

et al. 1997

The Journal of Veterinary Medical Science

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ABSTRACT. The conditioned suppression technique was employed to examine the acute effects of aspirin on auditory function in rats. Lever pressing behavior for water reinforcement was suppressed in the presence of an auditory stimulus that had been previously paired with electric shocks. A single intravenous injection of aspirin at a dose of 225 mg/kg caused an erroneous lever pressing response in the broad sound intensities of 2 kHz tone stimulus during the conditioned stimulus period. A statistically significant increase in the threshold for 2 kHz was found 1 to 72 hr after dosing but not for 4, 8 and 10 kHz. These results suggest that the hearing for low sound frequency in rats is vulnerable to the effects of aspirin. This paradigm in rats may be useful to further assess the different outer hair cells along the cochlear duct and provide an additional evidence for the aspirin ototoxicity research. -KEY WORDS: aspirin, conditioned suppression, hearing loss, low frequency, rat.J. Vet. Med. Sci. 59(10): 879-884, 1997 at the base and low frequencies at the apex [26]. Myers and Bernstein [27] reported that the hearing impairment induced by aspirin and salicylates in human does not depend on the sound frequency, but others have claimed that higher frequency is more susceptible to the effects of these drugs in human and/or guinea pigs [8,11,23]. Contrary to this, we recently reported that the hearing for lower frequency is more susceptible in the rat [22]. Most reports do agree that hearing loss and/or tinnitus are caused by aspirin; however, Boettcher and Salvi [2] reported that the results on the effects of aspirin on frequency selectivity are conflicting. To date, the ototoxicity of aspirin and/or salicylate has been assessed in guinea pigs [8,12,28], monkeys [27,30] or cats [14,15,31]. Rodents are preferable species, as the rat has an acoustic pathway similar to that of the cat and human [6,7,9], the experimental conditions for rodents are much more easily controlled and they are less expensive.If aspirin has a different effect at different OHCs along the cochlear duct, this may provide an additional approach for the aspirin ototoxicity research. In the present study of rats, to verify the results of our previous rat auditory brainstem response study [22], we first applied the conditioned suppression technique and then examined the effects of a single dose of aspirin on auditory stimulus-induced conditioned suppression, paying special attention to frequency selectivity. MATERIALS AND METHODS Animals and housing conditions:A total of 14 male Wistar SPF rats (CLEA Japan Inc., Japan) weighing 350 to 400 g were used. At the start of treatment, the animals were 20 weeks old. They were maintained on a mild waterdeprivation schedule to keep body weight at approximately 90% of the free-drinking levels throughout the pre-treatmentThe adverse effects, such as hearing loss and tinnitus, following the administration of aspirin and/or salicylates have long been known, and auditory impairment by these agents has been confirm...

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Electrophysiological Study of the Effect of Sodium Salicylate Upon the Cochlea

Cited by 39 publications

References 5 publications

Salicylate-induced changes in spontaneous activity of single units in the inferior colliculus of the guinea pig

Salicylate-induced changes in spontaneous activity of single units in the inferior colliculus of the guinea pig

A Characteristic of Aspirin-Induced Hearing Loss in Auditory Brainstem Response of Conscious Rats.

Frequency Selectivity on Aspirin-Induced Hearing Loss in Rats with Auditory Stimulus-Induced Conditioned Suppression.

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