TY - JOUR
T1 - Potential mechanisms underlying inflammation-enhanced aminoglycoside-induced cochleotoxicity
AU - Jiang, Meiyan
AU - Taghizadeh, Farshid
AU - Steyger, Peter S.
N1 - Funding Information:
This study was supported by R01 awards (DC004555, DC12588) from the National Institute of Deafness and Other Communication Disorders.
Publisher Copyright:
© 2017 Jiang, Taghizadeh and Steyger.
PY - 2017/11/21
Y1 - 2017/11/21
N2 - Aminoglycoside antibiotics remain widely used for urgent clinical treatment of lifethreatening 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 druginduced 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 druginduced hearing loss (and acute kidney damage) without compromising the life-saving bactericidal efficacy of aminoglycosides.
AB - Aminoglycoside antibiotics remain widely used for urgent clinical treatment of lifethreatening 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 druginduced 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 druginduced hearing loss (and acute kidney damage) without compromising the life-saving bactericidal efficacy of aminoglycosides.
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U2 - 10.3389/fncel.2017.00362
DO - 10.3389/fncel.2017.00362
M3 - Review article
AN - SCOPUS:85040938489
VL - 11
JO - Frontiers in Cellular Neuroscience
JF - Frontiers in Cellular Neuroscience
SN - 1662-5102
M1 - 362
ER -