Potential Mechanisms Underlying Inflammation-Enhanced Aminoglycoside-Induced Cochleotoxicity
Aminoglycoside antibiotics remain widely used for urgent clinical treatment of life-threatening infections, despite the well-recognized risk of permanent hearing loss, i.e., cochleotoxicity. Recent studies show that aminoglycoside-induced cochleotoxicity is exacerbated by bacteriogenic-induced infla...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-11-01
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| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fncel.2017.00362/full |
| _version_ | 1811282745149620224 |
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| author | Meiyan Jiang Farshid Taghizadeh Peter S. Steyger Peter S. Steyger |
| author_facet | Meiyan Jiang Farshid Taghizadeh Peter S. Steyger Peter S. Steyger |
| author_sort | Meiyan Jiang |
| collection | DOAJ |
| description | Aminoglycoside antibiotics remain widely used for urgent clinical treatment of life-threatening infections, despite the well-recognized risk of permanent hearing loss, i.e., cochleotoxicity. Recent studies show that aminoglycoside-induced cochleotoxicity is exacerbated by bacteriogenic-induced inflammation. This implies that those with severe bacterial infections (that induce systemic inflammation), and are treated with bactericidal aminoglycosides are at greater risk of drug-induced hearing loss than previously recognized. Incorporating this novel comorbid factor into cochleotoxicity risk prediction models will better predict which individuals are more predisposed to drug-induced hearing loss. Here, we review the cellular and/or signaling mechanisms by which host-mediated inflammatory responses to infection could enhance the trafficking of systemically administered aminoglycosides into the cochlea to enhance the degree of cochleotoxicity over that in healthy preclinical models. Once verified, these mechanisms will be potential targets for novel pharmacotherapeutics that reduce the risk of drug-induced hearing loss (and acute kidney damage) without compromising the life-saving bactericidal efficacy of aminoglycosides. |
| first_indexed | 2024-04-13T01:58:04Z |
| format | Article |
| id | doaj.art-4b16bf2932224ed8818031f4e3ff1755 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-13T01:58:04Z |
| publishDate | 2017-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-4b16bf2932224ed8818031f4e3ff17552022-12-22T03:07:43ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022017-11-011110.3389/fncel.2017.00362312551Potential Mechanisms Underlying Inflammation-Enhanced Aminoglycoside-Induced CochleotoxicityMeiyan Jiang0Farshid Taghizadeh1Peter S. Steyger2Peter S. Steyger3Oregon Hearing Research Center, Oregon Health & Science University, Portland, OR, United StatesOregon Hearing Research Center, Oregon Health & Science University, Portland, OR, United StatesOregon Hearing Research Center, Oregon Health & Science University, Portland, OR, United StatesNational Center for Rehabilitative Auditory Research, VA Portland Health Care System, Portland, OR, United StatesAminoglycoside antibiotics remain widely used for urgent clinical treatment of life-threatening infections, despite the well-recognized risk of permanent hearing loss, i.e., cochleotoxicity. Recent studies show that aminoglycoside-induced cochleotoxicity is exacerbated by bacteriogenic-induced inflammation. This implies that those with severe bacterial infections (that induce systemic inflammation), and are treated with bactericidal aminoglycosides are at greater risk of drug-induced hearing loss than previously recognized. Incorporating this novel comorbid factor into cochleotoxicity risk prediction models will better predict which individuals are more predisposed to drug-induced hearing loss. Here, we review the cellular and/or signaling mechanisms by which host-mediated inflammatory responses to infection could enhance the trafficking of systemically administered aminoglycosides into the cochlea to enhance the degree of cochleotoxicity over that in healthy preclinical models. Once verified, these mechanisms will be potential targets for novel pharmacotherapeutics that reduce the risk of drug-induced hearing loss (and acute kidney damage) without compromising the life-saving bactericidal efficacy of aminoglycosides.http://journal.frontiersin.org/article/10.3389/fncel.2017.00362/fullaminoglycosidesgentamicinototoxicitysepsisinfectionbacteriogenic |
| spellingShingle | Meiyan Jiang Farshid Taghizadeh Peter S. Steyger Peter S. Steyger Potential Mechanisms Underlying Inflammation-Enhanced Aminoglycoside-Induced Cochleotoxicity Frontiers in Cellular Neuroscience aminoglycosides gentamicin ototoxicity sepsis infection bacteriogenic |
| title | Potential Mechanisms Underlying Inflammation-Enhanced Aminoglycoside-Induced Cochleotoxicity |
| title_full | Potential Mechanisms Underlying Inflammation-Enhanced Aminoglycoside-Induced Cochleotoxicity |
| title_fullStr | Potential Mechanisms Underlying Inflammation-Enhanced Aminoglycoside-Induced Cochleotoxicity |
| title_full_unstemmed | Potential Mechanisms Underlying Inflammation-Enhanced Aminoglycoside-Induced Cochleotoxicity |
| title_short | Potential Mechanisms Underlying Inflammation-Enhanced Aminoglycoside-Induced Cochleotoxicity |
| title_sort | potential mechanisms underlying inflammation enhanced aminoglycoside induced cochleotoxicity |
| topic | aminoglycosides gentamicin ototoxicity sepsis infection bacteriogenic |
| url | http://journal.frontiersin.org/article/10.3389/fncel.2017.00362/full |
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