Post exposure administration of A1 adenosine receptor agonists attenuates noise-induced hearing loss

Wong, Ann Chi Yan; Guo, Cindy X.; Gupta, Rakesh; Housley, Gary D.; Thorne, Peter R.; Vlajkovic, Srdjan M.

doi:10.1016/j.heares.2009.12.004

Cited by 38 publications

(33 citation statements)

References 32 publications

(46 reference statements)

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“…Antioxidants, such as glutathione, d-methionine, ebselen, resveratrol and ascorbic acid, all attenuated NIHL in animal models when given before noise exposure 20 . In some studies, compounds such as A1 adenosine receptor agonists, ferulic acid, d-methionine and N-acetylcysteine attenuated NIHL when given up to 3 days after noise exposure [151][152][153][154] . Interestingly, polymorphisms in the gene encoding catalase have been linked to an increased susceptibility to NIHL in humans 27 , and mice that are heterozygous for a mutation in Sod1 show an increased vulnerability to NIHL 155 .…”

Section: Pharmacological Approachesmentioning

confidence: 99%

New treatment options for hearing loss

Müller

Barr-Gillespie

2015

Nat Rev Drug Discov

163

132

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Hearing loss is the most common form of sensory impairment in humans and affects more than 40 million people in the United States alone. No drug-based therapy has been approved by the Food and Drug Administration, and treatment mostly relies on devices such as hearing aids and cochlear implants. Over recent years, more than 100 genetic loci have been linked to hearing loss and many of the affected genes have been identified. This understanding of the genetic pathways that regulate auditory function has revealed new targets for pharmacological treatment of the disease. Moreover, approaches that are based on stem cells and gene therapy, which may have the potential to restore or maintain auditory function, are beginning to emerge.

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Section: Pharmacological Approachesmentioning

confidence: 99%

New treatment options for hearing loss

Müller

Barr-Gillespie

2015

Nat Rev Drug Discov

163

132

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“…In the cochlear partition, perfusion of adenosine in either perilymph or endolymph showed no changes in cochlear physiological parameters such as CAP [23,25] and no in vitro study has been published. However, Vlajkovic et al [42] (this issue; see also [43]) provides evidence that A1 receptor activation facilitates recovery from noise-induced hearing loss. In addition, prophylactic treatment with P1 receptor agonists confers otoprotection from noise damage [44,45].…”

Section: P1 Receptors In the Inner Earmentioning

confidence: 99%

Purinergic signaling in cochleovestibular hair cells and afferent neurons

Ito

Dulon

2010

Purinergic Signalling

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Purinergic signaling in the mammalian cochleovestibular hair cells and afferent neurons is reviewed. The scope includes P2 and P1 receptors in the inner hair cells (IHCs) of the cochlea, the type I spiral ganglion neurons (SGNs) that convey auditory signals from IHCs, the vestibular hair cells (VHCs) in the vestibular end organs (macula in the otolith organs and crista in the semicircular canals), and the vestibular ganglion neurons (VGNs) that transmit postural and rotatory information from VHCs. Various subtypes of P2X ionotropic receptors are expressed in IHCs as well as P2Y metabotropic receptors that mobilize intracellular calcium. Their functional roles still remain speculative, but adenosine 5′-triphosphate (ATP) could regulate the spontaneous activity of the hair cells during development and the receptor potentials of mature hair cells during sound stimulation. In SGNs, P2Y metabotropic receptors activate a nonspecific cation conductance that is permeable to large cations as NMDG + and TEA + . Remarkably, this depolarizing nonspecific conductance in SGNs can also be activated by other metabotropic processes evoked by acetylcholine and tachykinin. The molecular nature and the role of this depolarizing channel are unknown, but its electrophysiological properties suggest that it could lie within the transient receptor potential channel family and could regulate the firing properties of the afferent neurons. Studies on the vestibular partition (VHC and VGN) are sparse but have also shown the expression of P2X and P2Y receptors. There is still little evidence of functional P1 (adenosine) receptors in the afferent system of the inner ear.

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“…We have shown that the local or systemic administration of selective A 1 adenosine receptor (A 1 R) agonists, such as 2-chloro- N 6 -cyclopentyladenosine (CCPA) and adenosine amine congener (ADAC), can ameliorate cochlear injury and hearing loss following noise exposure [18, 19]. The important aspect of this finding is that the drugs were administered after the cessation of noise exposure, suggesting that A 1 R agonists could be useful for the treatment of acute noise-induced cochlear injury within a therapeutic window, and not only as prophylactics.…”

Section: Introductionmentioning

confidence: 99%

Adenosine Amine Congener as a Cochlear Rescue Agent

Vlajkovic

Chang

Paek

et al. 2014

BioMed Research International

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We have previously shown that adenosine amine congener (ADAC), a selective A1 adenosine receptor agonist, can ameliorate noise- and cisplatin-induced cochlear injury. Here we demonstrate the dose-dependent rescue effects of ADAC on noise-induced cochlear injury in a rat model and establish the time window for treatment. Methods. ADAC (25–300 μg/kg) was administered intraperitoneally to Wistar rats (8–10 weeks old) at intervals (6–72 hours) after exposure to traumatic noise (8–16 kHz, 110 dB sound pressure level, 2 hours). Hearing sensitivity was assessed using auditory brainstem responses (ABR) before and 12 days after noise exposure. Pharmacokinetic studies investigated ADAC concentrations in plasma after systemic (intravenous) administration. Results. ADAC was most effective in the first 24 hours after noise exposure at doses >50 μg/kg, providing up to 21 dB protection (averaged across 8–28 kHz). Pharmacokinetic studies demonstrated a short (5 min) half-life of ADAC in plasma after intravenous administration without detection of degradation products. Conclusion. Our data show that ADAC mitigates noise-induced hearing loss in a dose- and time-dependent manner, but further studies are required to establish its translation as a clinical otological treatment.

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Post exposure administration of A1 adenosine receptor agonists attenuates noise-induced hearing loss

Cited by 38 publications

References 32 publications

New treatment options for hearing loss

New treatment options for hearing loss

Purinergic signaling in cochleovestibular hair cells and afferent neurons

Adenosine Amine Congener as a Cochlear Rescue Agent

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