Aminoglycoside Antibiotics

Forge, Andrew; Schacht, Jochen

doi:10.1159/000013861

Cited by 592 publications

(553 citation statements)

References 144 publications

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“…The most parsimonious explanation for NIPTS in these mice was, therefore, OHC loss in the lower base and subtle OHC injury more apically. Within the cochlea, aminoglycosides preferentially injure the stria vascularis and outer hair cells (Taylor et al 2008;Rizzi and Hirose 2007;Forge and Schacht 2000). Although noise can also injure the stria, the injury appears largely reversible under all but the most extreme conditions Hirose and Liberman 2003), and it is not clear that lateral wall events can ultimately impact the extent of NIPTS (Ohlemiller 2008).…”

Section: Cells Impacted By Noise and Protected By Kmmentioning

confidence: 99%

“…Those that participate in the protection demonstrated here remain to be determined. KM affects multiple organs (Henley and Rybak 1995;Rizzi and Hirose 2007;Forge and Schacht 2000), where it may also elicit protective cascades, so that systemically mediated preconditioning influences cannot presently be ruled out.…”

Section: Sub-chronic Kanamycin As a Form Of Preconditioningmentioning

confidence: 99%

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Protection against Noise-Induced Hearing Loss in Young CBA/J Mice by Low-Dose Kanamycin

Fernandez

Ohlemiller

Gagnon

et al. 2010

JARO

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Animal studies indicate that a combination of kanamycin (KM) and noise produces a synergistic effect, whereby the threshold shift from the combination is greater than the sum of the shifts caused by either agent alone. Most such studies have focused on adult animals, and it has remained unclear whether younger, presumably more susceptible, animals show an even greater synergistic effect. The present study tested the hypothesis that young CBA/J mice receiving a low dose of KM (300 mg/kg, 2×/day, s.c.) from 20 to 30 days post-gestational age followed by brief noise exposure (110 dB SPL; 4-45 kHz, 30 s) would show greater noise-induced permanent threshold shifts (NIPTS) than mice receiving either treatment alone. Noise exposure produced 30-40 dB of NIPTS and moderate hair cell loss in young saline-treated mice. KM alone at this dose had no effect on thresholds. Surprisingly, mice receiving KM plus noise were protected from NIPTS, showing ABR thresholds not significantly different from unexposed controls. Mice receiving KM prior to noise exposure also showed significantly less outer hair cell loss than saline-treated mice. Additional experiments indicated protection by KM when the noise was applied either 24 or 48 h after the last KM injection. Our results demonstrate a powerful protective effect of subchronic low-dose kanamycin against NIPTS in young CBA/J mice. Repeated kanamycin exposure may establish a preconditioned protective state, the molecular bases of which remain to be determined.

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Section: Cells Impacted By Noise and Protected By Kmmentioning

confidence: 99%

Section: Sub-chronic Kanamycin As a Form Of Preconditioningmentioning

confidence: 99%

Protection against Noise-Induced Hearing Loss in Young CBA/J Mice by Low-Dose Kanamycin

Fernandez

Ohlemiller

Gagnon

et al. 2010

JARO

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“…The initial trigger of the toxic actions appears to be the formation of reactive oxygen species 1 subsequently invoking apoptotic or necrotic pathways. In cell or organ culture and with acute application of the drugs, apoptosis may be a predominant form of cell death.…”

Section: Introductionmentioning

confidence: 99%

Caspase-independent pathways of hair cell death induced by kanamycin in vivo

et al. 2005

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Cochlear and vestibular sensory cells undergo apoptosis when exposed to aminoglycoside antibiotics in organ culture, but mechanisms of chronic drug-induced hair cell loss in vivo are unclear. We investigated cell death pathways in a mouse model of progressive kanamycin-induced hair cell loss. Hair cell nuclei showed both apoptotic-and necrotic-like appearances but markers for classic apoptotic pathways (cytochrome c, caspase-9, caspase-3, JNK, TUNEL) were absent. In contrast, drug treatment caused EndoG translocation, activation of l-calpain, and both the synthesis and activation of cathepsin D. Poly (ADP-ribose) polymerase 1 (PARP1) was decreased, but a caspase-derived 89 kDa PARP1 fragment was not present. The mRNA level of PARP1 remained unchanged. Thus, chronic administration of aminoglycosides causes multiple forms of cell death, without a major contribution by classic apoptosis. These results provide a better understanding of the toxic effects of aminoglycosides and are relevant to design protection from aminoglycosideinduced hearing loss.

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“…Gentamicin causes renal injury after peritoneal injection in the goldfish, C. auratus (Liu et al, 2002). Nephrotoxicity and ototoxicity following aminoglycoside antibiotic treatment are well known in mammals (Dulon et al, 1988;Forge and Schacht, 2000). In guinea pigs, whilst nephrotoxicity can be reversible, inner ear lesions are permanent (Dulon et al, 1988;Hiel et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Effects of systemic versus local gentamicin on the inner ear in the Atlantic cod, Gadus morhua (L.), relevance for fish hearing investigations

et al. 2008

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a b s t r a c tFish models are increasingly being used for hearing research investigations. Aminoglycoside antibiotics that are used for damaging the inner ear hair cells can have systemic side effects leading to death of study animals. This study aimed to compare two methods: (i) systemic (intravenous) and (ii) local (intrasaccular) gentamicin administration for induction of inner ear hair cell damage in the Atlantic cod, Gadus morhua (L.). Hair cell damage was assessed using scanning electron microscopy; hair cell density, prevalence of immature hair cells and kinocilia length were measured. Gentamicin-treated fish were compared with control and sham fish. Intravenous gentamicin led to dose-dependent mortality caused by nephrotoxicity. The only visible effect after treatment was more immature hair cells and shorter kinocilia, the effect on hair cell density was equivocal. Following intrasaccular gentamicin treatment, fish mortality was negligible, and hair cells were damaged regardless of dose. Here, we observed decreased hair cell density, high prevalence of immature hair cells, and significantly shortened kinocilia. Conclusion: intrasaccular injection is preferable to intravenous injection of gentamicin for the study of ototoxicity in the Atlantic cod.

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Aminoglycoside Antibiotics

Cited by 592 publications

References 144 publications

Protection against Noise-Induced Hearing Loss in Young CBA/J Mice by Low-Dose Kanamycin

Protection against Noise-Induced Hearing Loss in Young CBA/J Mice by Low-Dose Kanamycin

Caspase-independent pathways of hair cell death induced by kanamycin in vivo

Effects of systemic versus local gentamicin on the inner ear in the Atlantic cod, Gadus morhua (L.), relevance for fish hearing investigations

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