N-Acetyl l-cysteine does not protect against premature age-related hearing loss in C57BL/6J mice: A pilot study

Davis, Roger T.; Kuo, Ming Wen; Stanton, Susan G.; Canlon, Barbara; Krieg, Edward F.; Alagramam, Kumar N.

doi:10.1016/j.heares.2006.07.003

Cited by 33 publications

(16 citation statements)

References 14 publications

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“…5g). One possible reason for such variable high frequency threshold elevation in prestin-CreER T2 –NN +/+ mice is the substantial contribution of C57BL6 strain background from the ACTG-Flpe deletor in the mixed background of prestin-CreER T2 –NN +/+ mice (Davis et al , 2007; Rodriguez et al , 2000; Spongr et al , 1997; Zheng et al , 1999). Regardless, most applications use either prestin-CreER T2 –or prestin-CreER T2 –NN +/− that all display normal hearing.…”

Section: Resultsmentioning

confidence: 99%

Outer hair cell‐specific prestin‐CreER^T2 knockin mouse lines

Fang

Zhang

Yamashita

et al. 2012

Genesis

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Outer hair cells (OHCs) in the cochlea are crucial for the remarkable hearing sensitivity and frequency tuning. To understand OHC physiology and pathology, it is imperative to use mouse genetic tools to manipulate gene expression specifically in OHCs. Here, we generated 2 prestin knockin mouse lines: 1) the prestin-CreERT2 line, with an internal ribosome entry site (IRES)-CreERT2-FRT-Neo-FRT cassette inserted into the prestin locus after the stop codon, and 2) the prestin-CreERT2-NN line, with the FRT-Neo-FRT removed subsequently. We characterized the inducible Cre activity of both lines by crossing them with the reporter lines CAG-eGFP and Ai6. Cre activity was induced with tamoxifen at various postnatal ages and only detected in OHCs, resembling the endogenous prestin expression pattern. Moreover, prestin-CreERT2 +/− (heterozygotes) and +/+ (homozygotes) as well as prestin-CreERT2-NN +/− mice displayed normal hearing. These 2 prestin-CreERT2 mouse lines are therefore useful tools to analyze gene function in OHCs in vivo.

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Section: Resultsmentioning

confidence: 99%

Outer hair cell‐specific prestin‐CreER^T2 knockin mouse lines

Fang

Zhang

Yamashita

et al. 2012

Genesis

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“…First, L-NAC showed no protection again age-related hearing loss in mice [14]. Blakley et al [15] reviewed differences between species highlighting the differences in ototoxic dose for gentamicin and cisplatin between mice and guinea pigs.…”

Section: Discussionmentioning

confidence: 99%

N-Acetyl L-Cysteine does not protect mouse ears from the effects of noise*

Davis

Custer

Krieg

et al. 2010

Journal of Occupational Medicine and Toxicology

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BackgroundNoise-induced hearing loss (NIHL) is one of the most common occupational injuries in the United States. It would be extremely valuable if a safe, inexpensive compound could be identified which protects worker hearing from noise. In a series of experiments, Kopke has shown that the compound N-acetyl-L-cysteine (L-NAC) can protect the hearing of chinchillas from the effects of a single exposure to noise. L-NAC is used in clinical medicine and is very safe. Although L-NAC was reported to be promising, it has not been successful in other studies (Kramer et al., 2006; Hamernik et al., 2008). The present study was undertaken to determine if L-NAC could protect C57BL/6J (B6) mice from the permanent effects of noise.MethodTwo groups of five B6 mice were injected with either 300 or 600 mg/kg L-NAC approximately 1 hr prior to a 104 dB broadband noise exposure and again immediately after the exposure. A control group (N = 7) was exposed to the same noise level but injected with vehicle (sterile saline). Auditory brainstem response measurements were made at 4, 8, 16 and 32 kHz one week prior to and 12 days after exposure.ConclusionsThere were no statistically significant differences in ABR threshold shifts between the mice receiving L-NAC and the control mice. This indicates that L-NAC was not effective in preventing permanent threshold shift in this mouse model of NIHL.

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“…Yet it has not been utilized successfully in protection against ARHL in either the C57BL/6J mouse (Davis et al, 2007) or the F344/NHsd rat (Bielefeld et al, 2008). It must be noted, though, that unsuccessful studies of pharmacological protection from acquired hearing loss are complicated by numerous factors related to dosing levels, frequency of dosing, etc, and do not extinguish the possibility that a particular drug (in this case, L-NAC) can be used as a successful prevention against ARHL.…”

Section: Strategies For Preventing or Treating Arhlmentioning

confidence: 99%

Age-related hearing loss: Is it a preventable condition?

et al. 2010

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Numerous techniques have been tested to attempt to prevent the onset or progression of age-related hearing loss (ARHL): raising the animals in an augmented acoustic environment (used successfully in mouse and rat models), enhancing the antioxidant defenses with exogenous antioxidant treatments (used with mixed results in mouse and rat models), raising the animals with a calorie restricted diet (used successfully in mouse and rat models), restoring lost endocochlear potential voltage with exogenous electrical stimulation (used successfully in the Mongolian gerbil model), and hypothetical enhancement of outer hair cell electromotility with salicylate therapy. Studies of human ARHL have revealed a set of unique hearing loss configurations with unique underlying pathologies. Animal research has developed models for the different forms of age-related peripheral pathology. Using the animal models, different techniques for prevention of ARHL have been developed and tested. The current review discusses ARHL patterns in humans and animal models, followed by discussions of the different prevention techniques.

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N-Acetyl l-cysteine does not protect against premature age-related hearing loss in C57BL/6J mice: A pilot study

Cited by 33 publications

References 14 publications

Outer hair cell‐specific prestin‐CreER^T2 knockin mouse lines

Outer hair cell‐specific prestin‐CreER^T2 knockin mouse lines

N-Acetyl L-Cysteine does not protect mouse ears from the effects of noise*

Age-related hearing loss: Is it a preventable condition?

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N-Acetyl l-cysteine does not protect against premature age-related hearing loss in C57BL/6J mice: A pilot study

Cited by 33 publications

References 14 publications

Outer hair cell‐specific prestin‐CreERT2 knockin mouse lines

Outer hair cell‐specific prestin‐CreERT2 knockin mouse lines

N-Acetyl L-Cysteine does not protect mouse ears from the effects of noise*

Age-related hearing loss: Is it a preventable condition?

Contact Info

Product

Resources

About

Outer hair cell‐specific prestin‐CreER^T2 knockin mouse lines

Outer hair cell‐specific prestin‐CreER^T2 knockin mouse lines