Aspirin to Prevent Gentamicin-Induced Hearing Loss

Sha, Su Hua; Qiu, Jianyin; Schacht, Jochen

doi:10.1056/nejmc053428

Cited by 160 publications

(113 citation statements)

References 3 publications

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“…While many drugs have been demonstrated to successfully protect hair cells against damage (e.g., antioxidants, caspase inhibitors, Stat-1, etc. ; Matsui et al 2002;Wang et al 2003Wang et al , 2004Sha et al 2006;Campbell et al 2007;Schmitt et al 2009), there is currently no FDA-approved drug used for the prevention of hearing loss. Aspirin was demonstrated to protect against aminoglycoside-induced hair cell death (Sha et al 2006), but required high daily doses (3 g/day).…”

Section: Introductionmentioning

confidence: 99%

“…; Matsui et al 2002;Wang et al 2003Wang et al , 2004Sha et al 2006;Campbell et al 2007;Schmitt et al 2009), there is currently no FDA-approved drug used for the prevention of hearing loss. Aspirin was demonstrated to protect against aminoglycoside-induced hair cell death (Sha et al 2006), but required high daily doses (3 g/day). With evidence now that inhibition of one cell death pathway can lead to upregulation of other death pathways, the hypothesis that hair cells will "find a way to die" seems likely (Lin et al 1999;Yu et al 2004;Vandenabeele et al 2006).…”

Section: Introductionmentioning

confidence: 99%

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Quinoline Ring Derivatives Protect Against Aminoglycoside-Induced Hair Cell Death in the Zebrafish Lateral Line

Keating

et al. 2012

JARO

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We have previously published results from a screen of 1,040 FDA-approved drugs and bioactives (NINDS Custom Collection) for drugs that protect against neomycin-induced hair cell death (Ou et al., J Assoc Res Otolaryngol 10:191-203, 2009). Further evaluation of this drug library identified eight protective drugs that shared a common quinoline scaffold. These drugs were tested further in terms of their protection against other aminoglycosides, as well as their effect on aminoglycoside uptake. All of the eight quinolines that protected against neomycin were found to protect against shortand long-term gentamicin damage protocols. We then tested the structurally related compounds quinoline, isoquinoline, naphthalene, and indole for protective effects. Of these compounds, indole demonstrated a small but significant amount of protection against neomycin, while quinoline and isoquinoline partially protected against long-term gentamicin damage. We examined whether the protective activity of this group of compounds was related to known targets of the quinoline derivatives. The protective effects did not seem linked to either the cholinergic or histaminergic pathways that are regulated by some members of the quinoline family. However, all eight protective drugs were found to reduce the uptake of aminoglycosides into hair cells. Subsequent experiments suggest that reduction of uptake is the primary mechanism of protection among the quinoline drugs.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Quinoline Ring Derivatives Protect Against Aminoglycoside-Induced Hair Cell Death in the Zebrafish Lateral Line

Keating

et al. 2012

JARO

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“…The data from two clinical trials, using aspirin as an investigational agent, clearly confirm the promise of antioxidant agents for reducing drug-induced hearing loss in human patients that require these agents for their life-saving therapeutic benefit (Sha et al 2006;Behnoud et al 2009). The data presented here document preservation of hair cells, and protection of auditory thresholds, in two different guinea pig strains, tested in two different laboratories, using an oral nutrient supplement.…”

Section: Figmentioning

confidence: 88%

“…There are now a variety of drugs and other substances that have been shown to effectively attenuate cell death and hearing loss after gentamicin insult, although complete protection has been elusive (for summary, see Table 1). In the first human interventions, aspirin reduced gentamicin-induced hearing loss in human patients in China (Sha et al 2006), an effect that has since been confirmed in a second patient population in Saudi Arabia (Behnoud et al 2009). However, gastric events were an adverse side effect for some patients.…”

Section: Introductionmentioning

confidence: 95%

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Assessment of Nutrient Supplement to Reduce Gentamicin-Induced Ototoxicity

Prell

Ojano-Dirain

Rudnick

et al. 2014

JARO

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Gentamicin is an aminoglycoside antibiotic used to treat gram-negative bacterial infections. Treatment with this antibiotic carries the potential for adverse side effects, including ototoxicity and nephrotoxicity. Ototoxic effects are at least in part a consequence of oxidative stress, and various antioxidants have been used to attenuate gentamicin-induced hair cell death and hearing loss. Here, a combination of nutrients previously shown to reduce oxidative stress in the hair cells and attenuate hearing loss after other insults was evaluated for potential protection against gentamicin-induced ototoxicity. Guinea pigs were maintained on a nutritionally complete standard laboratory animal diet or a diet supplemented with β-carotene, vitamins C and E, and magnesium. Three diets with iterative increases in nutrient levels were screened; the final diet selected for study use was one that produced statistically reliable increases in plasma levels of vitamins C and E and magnesium. In two separate studies, significant decreases in gentamicin-induced hearing loss at frequencies including 12 kHz and below were observed, with less benefit at the higher frequencies. Consistent with the functional protection, robust protection of both the inner and outer hair cell populations was observed, with protection largely in the upper half of the cochlea. Protection was independently assessed in two different laboratories, using two different strains of guinea pigs. Additional in vitro tests did not reveal any decrease in antimicrobial activity with nutrient additives. Currently, there are no FDA-approved treatments for the prevention of gentamicin-induced ototoxicity. The current data provide a rationale for continued investigations regarding translation to human patients.

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Low-Dose Aspirin and Progression of Age-Related Hearing Loss

Clark,

Zhou,

Hussain

et al. 2024

JAMA Netw Open

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ImportanceAge-related hearing loss is common in an aging population, affecting communication and contributing to a worsened quality of life. It occurs as a result of cochlear degeneration and may be further exacerbated by inflammation and microvascular changes, as observed in animal models.ObjectiveTo compare the effect of daily low-dose aspirin vs placebo on the progression of age-related hearing loss in healthy older adults.Design, Setting, and ParticipantsA prespecified secondary analysis was conducted of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized clinical trial. Participants were 279 healthy community-dwelling individuals living in Australia who were aged 70 years or older and free of overt cardiovascular diseases, dementia, and life-limiting illnesses. Participants were recruited between January 1, 2010, and December 31, 2014, and followed up over 3 years. Statistical analysis was completed from June to December 2023.InterventionA 100-mg daily dose of enteric-coated aspirin or matching placebo.Main Outcomes and MeasuresHearing measures were air conduction audiometry and binaural speech perception in noise. Assessments were conducted at baseline, 18 months, and 3 years. The change from baseline hearing measures were analyzed using an intention to treat approach. Aspirin and placebo were compared using mixed linear regression models adjusting for age, sex, diabetes, and smoking.ResultsOf 279 participants, 154 (55%) were male, and the median age at baseline was 73.1 years (IQR, 71.5-76.2 years). A total of 98 of 138 participants (71%) in the aspirin group and 94 of 141 participants (67%) in the placebo group reported experiencing hearing loss at baseline. Compared with placebo, aspirin did not affect the changes in mean (SD) 4-frequency average hearing threshold from baseline to year 3 (aspirin: baseline, 27.8 [13.3] dB; year 3, 30.7 [13.7] dB; difference, 3.3 [3.9] dB; placebo: baseline, 27.5 [12.6] dB; year 3, 30.9 [13.8] dB; difference, 3.0 [4.8] dB; P = .55) nor any other tested frequencies. An increase in air conduction threshold indicates a deterioration in hearing. Similarly, for the mean (SD) speech reception threshold, there was no significant difference observed between the aspirin and placebo group at the year 3 follow-up assessment (aspirin: baseline, –9.9 [3.8] dB; year 3, –9.1 [3.8] dB; difference, 0.9 [2.9] dB; placebo: baseline, –10.5 [7.1] dB; year 3, –9.6 [4.1] dB; difference, 0.9 [5.9] dB; P = .86). The findings were consistent across sex, age groups, diabetic and smoking status.Conclusions and RelevanceIn this secondary analysis of the ASPREE randomized clinical trial, low-dose aspirin did not affect the progression of age-related hearing loss. More investigation is warranted on whether a longer follow-up or the use of a more powerful anti-inflammatory agent might prove beneficial.Trial Registrationanzctr.org.au Identifier: ACTRN12614000496617

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Aspirin to Prevent Gentamicin-Induced Hearing Loss

Cited by 160 publications

References 3 publications

Quinoline Ring Derivatives Protect Against Aminoglycoside-Induced Hair Cell Death in the Zebrafish Lateral Line

Quinoline Ring Derivatives Protect Against Aminoglycoside-Induced Hair Cell Death in the Zebrafish Lateral Line

Assessment of Nutrient Supplement to Reduce Gentamicin-Induced Ototoxicity

Low-Dose Aspirin and Progression of Age-Related Hearing Loss

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