The vascular component of sodium salicylate ototoxicity in the guinea pig

Anne Didier, Josef M. Miller, Alfred Nuttall

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Drugs of the salicylate family (aspirin-like drugs) are reversibly ototoxic. Electrophysiologic and ultrastructural evidence suggests an impairment of the sensory hair cells of the cochlea following salicylate treatment. In addition, since these drugs can cause vasoconstriction, the ototoxicity of salicylates may also involve an impairment of the blood circulation in inner ear. However, a vascular hypothesis of salicylate toxicity has not received much attention. In the current study, we simultaneously measured cochlear blood flow (by laser Doppler flowmetry) and the sound-evoked potentials from the round window. Sodium salicylate caused a decrease in cochlear blood flow that appeared within 30 min following an intramuscular injection of a low dose of sodium salicylate (100 mg/kg). This sodium salicylate dose did not cause a change in auditory sensitivity. For higher doses (200 mg/kg and 300 mg/kg), both cochlear blood flow and auditory sensitivity were affected. The 300 mg/kg dose decreased blood flow by about 25% and elevated compound action potential thresholds by 10 to 25 dB for high frequencies (≥ 8 kHz). Further experiments showed that salicylate-induced threshold shifts were significantly reduced for the mid-frequencies when cochlear blood flow is increased by the vasodilating drug hydralazine (negating the flow reduction caused by salicylate). These data indicate that in addition to the direct effect of systemically administered salicylate on neurosensory function a decreased blood flow contributes to the ototoxicity of salicylates.

Original languageEnglish (US)
Pages (from-to)199-206
Number of pages8
JournalHearing Research
Volume69
Issue number1-2
DOIs
StatePublished - 1993
Externally publishedYes

Fingerprint

Sodium Salicylate
Salicylates
Blood Vessels
Guinea Pigs
Cochlea
Pharmaceutical Preparations
Hydralazine
Laser-Doppler Flowmetry
Blood Circulation
Intramuscular Injections
Inner Ear
Vasoconstriction
Evoked Potentials
Aspirin
Action Potentials

Keywords

  • Cochlea
  • Guinea pig
  • Hydralazine
  • Laser doppler flowmetry
  • Sodium salicylate
  • Topical drug application

ASJC Scopus subject areas

  • Sensory Systems

Cite this

The vascular component of sodium salicylate ototoxicity in the guinea pig. / Didier, Anne; Miller, Josef M.; Nuttall, Alfred.

In: Hearing Research, Vol. 69, No. 1-2, 1993, p. 199-206.

Research output: Contribution to journalArticle

Didier, Anne ; Miller, Josef M. ; Nuttall, Alfred. / The vascular component of sodium salicylate ototoxicity in the guinea pig. In: Hearing Research. 1993 ; Vol. 69, No. 1-2. pp. 199-206.
@article{eb95d4bc760e486ead9737373434b0fa,
title = "The vascular component of sodium salicylate ototoxicity in the guinea pig",
abstract = "Drugs of the salicylate family (aspirin-like drugs) are reversibly ototoxic. Electrophysiologic and ultrastructural evidence suggests an impairment of the sensory hair cells of the cochlea following salicylate treatment. In addition, since these drugs can cause vasoconstriction, the ototoxicity of salicylates may also involve an impairment of the blood circulation in inner ear. However, a vascular hypothesis of salicylate toxicity has not received much attention. In the current study, we simultaneously measured cochlear blood flow (by laser Doppler flowmetry) and the sound-evoked potentials from the round window. Sodium salicylate caused a decrease in cochlear blood flow that appeared within 30 min following an intramuscular injection of a low dose of sodium salicylate (100 mg/kg). This sodium salicylate dose did not cause a change in auditory sensitivity. For higher doses (200 mg/kg and 300 mg/kg), both cochlear blood flow and auditory sensitivity were affected. The 300 mg/kg dose decreased blood flow by about 25{\%} and elevated compound action potential thresholds by 10 to 25 dB for high frequencies (≥ 8 kHz). Further experiments showed that salicylate-induced threshold shifts were significantly reduced for the mid-frequencies when cochlear blood flow is increased by the vasodilating drug hydralazine (negating the flow reduction caused by salicylate). These data indicate that in addition to the direct effect of systemically administered salicylate on neurosensory function a decreased blood flow contributes to the ototoxicity of salicylates.",
keywords = "Cochlea, Guinea pig, Hydralazine, Laser doppler flowmetry, Sodium salicylate, Topical drug application",
author = "Anne Didier and Miller, {Josef M.} and Alfred Nuttall",
year = "1993",
doi = "10.1016/0378-5955(93)90108-D",
language = "English (US)",
volume = "69",
pages = "199--206",
journal = "Hearing Research",
issn = "0378-5955",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - The vascular component of sodium salicylate ototoxicity in the guinea pig

AU - Didier, Anne

AU - Miller, Josef M.

AU - Nuttall, Alfred

PY - 1993

Y1 - 1993

N2 - Drugs of the salicylate family (aspirin-like drugs) are reversibly ototoxic. Electrophysiologic and ultrastructural evidence suggests an impairment of the sensory hair cells of the cochlea following salicylate treatment. In addition, since these drugs can cause vasoconstriction, the ototoxicity of salicylates may also involve an impairment of the blood circulation in inner ear. However, a vascular hypothesis of salicylate toxicity has not received much attention. In the current study, we simultaneously measured cochlear blood flow (by laser Doppler flowmetry) and the sound-evoked potentials from the round window. Sodium salicylate caused a decrease in cochlear blood flow that appeared within 30 min following an intramuscular injection of a low dose of sodium salicylate (100 mg/kg). This sodium salicylate dose did not cause a change in auditory sensitivity. For higher doses (200 mg/kg and 300 mg/kg), both cochlear blood flow and auditory sensitivity were affected. The 300 mg/kg dose decreased blood flow by about 25% and elevated compound action potential thresholds by 10 to 25 dB for high frequencies (≥ 8 kHz). Further experiments showed that salicylate-induced threshold shifts were significantly reduced for the mid-frequencies when cochlear blood flow is increased by the vasodilating drug hydralazine (negating the flow reduction caused by salicylate). These data indicate that in addition to the direct effect of systemically administered salicylate on neurosensory function a decreased blood flow contributes to the ototoxicity of salicylates.

AB - Drugs of the salicylate family (aspirin-like drugs) are reversibly ototoxic. Electrophysiologic and ultrastructural evidence suggests an impairment of the sensory hair cells of the cochlea following salicylate treatment. In addition, since these drugs can cause vasoconstriction, the ototoxicity of salicylates may also involve an impairment of the blood circulation in inner ear. However, a vascular hypothesis of salicylate toxicity has not received much attention. In the current study, we simultaneously measured cochlear blood flow (by laser Doppler flowmetry) and the sound-evoked potentials from the round window. Sodium salicylate caused a decrease in cochlear blood flow that appeared within 30 min following an intramuscular injection of a low dose of sodium salicylate (100 mg/kg). This sodium salicylate dose did not cause a change in auditory sensitivity. For higher doses (200 mg/kg and 300 mg/kg), both cochlear blood flow and auditory sensitivity were affected. The 300 mg/kg dose decreased blood flow by about 25% and elevated compound action potential thresholds by 10 to 25 dB for high frequencies (≥ 8 kHz). Further experiments showed that salicylate-induced threshold shifts were significantly reduced for the mid-frequencies when cochlear blood flow is increased by the vasodilating drug hydralazine (negating the flow reduction caused by salicylate). These data indicate that in addition to the direct effect of systemically administered salicylate on neurosensory function a decreased blood flow contributes to the ototoxicity of salicylates.

KW - Cochlea

KW - Guinea pig

KW - Hydralazine

KW - Laser doppler flowmetry

KW - Sodium salicylate

KW - Topical drug application

UR - http://www.scopus.com/inward/record.url?scp=0027275295&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027275295&partnerID=8YFLogxK

U2 - 10.1016/0378-5955(93)90108-D

DO - 10.1016/0378-5955(93)90108-D

M3 - Article

C2 - 8226340

AN - SCOPUS:0027275295

VL - 69

SP - 199

EP - 206

JO - Hearing Research

JF - Hearing Research

SN - 0378-5955

IS - 1-2

ER -