Therapeutic Prevention of Acquired Hearing LossMelanie McQueen, B.S. and Annelise Gerardi, B.H.S.The University of Texas at AustinSchool of Communication Sciences of Disorders

Overview● Introduction to Oxidative Stress● Role of Oxidative Stress in Acquired

Hearing Loss● Antioxidant Prevention of

Noise-Induced Hearing Loss

Acquired Hearing Loss● Oxidative Stress (free radical

formation)● Types of hearing loss driven by

oxidative stress: ○ Noise-Induced Hearing Loss (NIHL) ○ Drug-Induced Hearing Loss○ Age-Induced Hearing Loss

● NIHL is the most responsive to therapeutic treatment

What Causes NIHL?● Mechanical damage● Ischemia● Oxidative stress

○ Free radical formation in Organ of Corti = death of hair cells

Strategies for Reducing NIHL● Reduce the sound level at the source● Reduce time of exposure to the source● Design better hearing protection

devices● Decrease oxidative stress that induces

cell death in the inner ear through drugs or dietary supplements

Article One: Post-exposure treatment attenuates noise-induced hearing lossNeuroscience (2005)D. Yamashita, H.Y. Jiang, C. Le Prell, J. Schacht, and J. Miller

Background● Free radical formation can occur up to

10 days after noise exposure● Can antioxidant intervention during this

period reduce NIHL?● Can antioxidant intervention during this

period reduce NIHL?

Subjects● 42 male guinea pigs● Divided into 7 groups:Group 1 Group 2 Group 3 Group 4 Group 5 Group 6 Group 7

Control Saline injected on Day 1 (3 days before noise exposure)

Salicylate + trolox injected Days 1 to 14

Salicylate + trolox injected 1 hour after noise exposure until Day 14

Salicylate + trolox injected 1 day after noise exposure until Day 14

Salicylate + trolox injected 3 days after noise exposure until Day 14

Salicylate + trolox injected 5 days after noise exposure until Day 14

*Trolox = 50mg/kg, twice daily*Salicylate = 75 mg/kg, twice daily

Method● Animals in all groups were subjected to

noise on Day 4.● Stimulus = One-octave band noise

centered at 4 kHz @ 120 dB SPL for 5 hours

Outcome Measures● ABR Thresholds:

○ ABR thresholds at 4, 8, and 16 kHz were measured 7 days before treatment and 10 days after noise exposure

● Histological Examinations:○ Left ears processed for histological

hair cell counts○ Right ears processed for

immunohistochemical staining

Results● Reduction in NIHL threshold shift was

directly related to onset of preventative drug treatment

● Effectiveness of treatment decreased with time after noise exposure

Noise-induced ABR Threshold Shifts

Histological Hair Cell Counts

Immunohistochemical Staining in the Organ of Corti

Immunohistochemical Staining in the Organ of Corti

Immunohistochemical Staining in the Organ of Corti

Immunohistochemical Staining in the Organ of Corti

Discussion● NIHL and sensory cell death can be

attenuated up to 3 days after noise exposure using a combination of antioxidants (salicylate + trolox)

● Pretreatment was most effective● In general, free radical formation was

reduced in cochlear cells by antioxidant therapy.

Implications● NIHL is a major cause of acquired

hearing loss in the world● Complete elimination of mechanical

cochlear damage and avoidance of acute accidental noise is impractical

● Therefore, could antioxidant treatment within a time window of noise exposure reduce NIHL in humans?

Article Two: Increased vitamin plasma levels in Swedish military personnel treated with nutrients prior to automatic weapon training Noise Health (2011)C. Le Prell, C. Johnson, A. Lindblad, A ̊. Skjo ̈nsberg, M. Ulfendahl, K. Guire, G. Green, M. Campbell, and J Miller

Background● The previous study demonstrated the

effectiveness of combined antioxidants in the prevention of NIHL in guinea pigs

● Can antioxidant treatment translate to the prevention of NIHL in humans?

Subjects● 31 subjects:

○ 10 Swedish military officers○ 21 Swedish military academy trainees

● Advertisements posted on base to encourage people to participate

● Exclusion factors: ○ Gastrointenstinal disturbances, neurological

disturbances, hematological disorders, and auditory/vestibular issues

● Requirements: ○ Symmetrical normal hearing, Type A tymps,

ipsilateral reflexes, and threshold asymmetry at </ 15 dB at all frequencies

Treatment● Micronutrient treatment combination

of beta carotene, vitamin C, vitamin E, and magnesium in the form of a pill

● Dosage was 6 pills a day (3 at a time, twice daily)

Study Design ● Double blind study● Randomized - Subjects

received nutrient or placebo condition for “Arm 1”

○ Each “arm” consisted of a single weapons training class

○ For “Arm 2,” there was a washout period before switching to other pill

Outcome Measures● Questionnaire

○ Self-reporting Hearing and Tinnitus survey

● Otoscopy● Tympanometry● Reflex Testing at 1 kHz @ 100 dB HL● Pure Tone Audiometry● DPOAE’s

Outcome Measures● Noise Exposure levels:

○ 40 shots fired from automatic machine gun in a bunker for over 1 minute while standard hearing protection was worn

● Blood Sampling and Analysis: ○ Collected from 9/10 of the officers○ Levels for vitamin C, vitamin E, beta

carotene and magnesium were measured

○ Taken one day before testing and 2 hours after exposure

Results:● Adverse effects:

○ One subject reported queziness within one day of study. 2 reported feeling ill during or after treatment

● Plasma levels: ○ Post treatment, levels increased for all except

magnesium

○ No reliable change in plasma levels when placebo was consumed first

● Pre 1 Test Outcomes: ○ Minimal differences seen between soldiers and

officers relating to age or effect

● Pre 2 Test Outcomes: ○ No effects on baseline measures

Results● Audiometry:

○ No effect on baseline thresholds thus no opportunity to measure protection against TTS as a function of treatment

● Tinnitus: ○ Reported sporadically, but not

significant

● Treatment group showed a 4-12 dB smaller TTS than placebo group for within subject comparisons

Measured Antioxidant Levels Before and 2 Hours Post Exposure for Placebo and Non Placebo Groups

Black = Pre Gray = Post

Threshold Shift Changes

Within 15 Minutes of Loud Noise Exposure

Threshold Shift

Changes within Two

Days of Treatment

Discussion● No consistency in results

● No reliable noise-induced threshold shift was measured for either the placebo or non-placebo group

○ Does not support use of a preventative drug for human hearing protection

● However, elevated plasma levels were found in the blood of participants, which could be helpful for future studies

Discussion● Ear protection was good for avoiding

NIHL in humans...○ However, it created a lack of noise

induced changes, so it could not be determined if nutrients have beneficial effects in relation to hearing loss

● Need to design better studies in order to obtain successful human trials

Questions?

Sources:Yamashita D; Jiang HY; Le Prell CG; Schacht J; Miller

JM, Neuroscience [Neuroscience], ISSN: 0306-4522, 2005; Vol. 134 (2), pp. 633-42; Publisher: Elsevier Science; PMID: 15961244, Database: MEDLINE

Le Prell CG; Johnson AC; Lindblad AC; Skjönsberg A; Ulfendahl M; Guire K; Green GE; Campbell KC; Miller JM, Noise & Health [Noise Health], ISSN: 1463-1741, 2011 Nov-Dec; Vol. 13 (55), pp. 432-43; Publisher: Medknow Publications Pvt. Ltd; PMID: 22122960, Database: MEDLINE