Genetic aspects of antibiotic induced deafness: mitochondrial inheritance.

Hu, Dongxue; Qui, Weimin; Wu, Bifeng; Fang, Lijun; Zhou, Fei; Gu, Yingchun; Zhang, Q H; Yan, Jiang-Wei; Ding, Yonghe; Wong, Heidi W. S.

doi:10.1136/jmg.28.2.79

Cited by 157 publications

(86 citation statements)

References 14 publications

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“…The fact that NRTIs were capable of interacting synergistically with the loud sounds associated with the noise exposure of the present study is consistent with the known effects of mitochondrial defects on hearing. Specifically, mitochondrial DNA mutations have been linked to a number of different causes of hearing loss including syndromic deafness, non-syndromic deafness, presbycusis, and a genetic susceptibility to ototoxicity (Higashi 1989;Hu et al 1991;Hutchin and Cortopassi 2000;Fischel-Ghodsian 2003;Xhing et al 2007). …”

Section: Discussionmentioning

confidence: 99%

Noise-induced hearing loss in mice treated with antiretroviral drugs

et al. 2008

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The results reported here for CBA/CaJ mice describe the effects of regular dosing with a common antiretroviral drug combination on outer hair cell (OHC) function using measures of 2f 1 -f 2 distortion product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs). Specifically, experimental mice were treated daily over a 3-mo period with the nucleoside reverse transcriptase inhibitors (NRTIs), zidovudine (ZDV) and lamivudine (3TC), dissolved in their drinking water, while their control counterparts received untreated water. DPOAE levels and ABR detection thresholds prior to and after 12 wk of NRTI treatment did not differ between experimental and control groups. To assess whether NRTI treatment potentiates the adverse effects of noise overexposure on OHC function, both experimental and control mice were exposed 1 wk later, while still on the drug regimen, to a 10-kHz octave-band noise (OBN) at 105 dB SPL for 1 h. A major outcome of the sound overexposure episode was that the NRTI-pretreated mice showed significantly greater permanent OBNinduced reductions in DPOAE levels at 2 wk postexposure than were observed for the untreated control animals. These findings support the notion that a synergistic relationship exists between certain NRTIs and intense sounds in that such preexposure drug treatments produced greater noiseinduced decreases in DPOAE activity than did noise exposure alone. This drug/noise interaction is consistent with the known harmful effects of NRTIs on cellular mitochondrial activity.

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Section: Discussionmentioning

confidence: 99%

Noise-induced hearing loss in mice treated with antiretroviral drugs

et al. 2008

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“…Our experiments did not directly address the possible roles of mitochondria in the production of free radicals. However, clinical epidemiological studies have elucidated a compelling hypothesis of mitochondrial dysfunction as a mechanism or co-factor in aminoglycoside ototoxicity (Hu et al, 1991;Jaber et al, 1992;Fischel-Ghodsian et al, 1993;Ouweland et al, 1992;Cortopassi and Hutchin, 1994). Several groups have determined that a gene conferring extreme sensitivity to aminoglycoside is carried exclusively via maternal inheritance.…”

Section: Mitochondrial Dysfunction and Free Radical Production In Amimentioning

confidence: 99%

Reactive oxygen species in chick hair cells after gentamicin exposure in vitro

1997

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Reactive oxygen species have been invoked as a causative agent of cell death in many different developmental and pathological states. The presence of free radicals and their importance in hair cell death due to aminoglycosides is suggested by a number of studies that have demonstrated a protective effect of antioxidants. By using dichlorofluorescin (DCFH) a fluorescent compound that is a reporter of reactive oxygen species, we have shown that free radicals are rapidly produced by avian hair ceils in vitro after exposure to gentamicin. In addition, free radical scavengers, catalase and glutathione, were tested with DCFH fluorescent imaging for their ability to quench the production of reactive oxygen species in hair cells after drug exposure. Both free radical scavengers were very effective in suppressing drug-induced production of free radicals. Next, we investigated the ability of these antioxidants to preserve the structural integrity of hair cells after exposure to gentamicin. We were not able to detect any attenuation of the hair cell loss using antioxidants in conjunction with gentamicin. This result must be qualified by the fact that the antioxidants used were not effective over long-term gentamicin exposure. Therefore, methodological constraints prevented adequately testing possible protective effects of free radical scavengers in this model system.

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“…This rare trait of hypersensitivity was found to be transmitted through the maternal lineage in 41 human pedigrees (10,12).…”

Section: Aminoglycoside Hypersensitivity In Humans Is a Maternally Inmentioning

confidence: 99%