Protective Effect of Pentoxifylline on Amikacin-Induced Ototoxicity

El‐Anwar, Mohammad Waheed; Abdelmonem, Said; Nada, Ebtessam; Galhoom, Dalia; Abdelsameea, Ahmed A.

doi:10.1177/014556131809700802

Cited by 4 publications

(3 citation statements)

References 20 publications

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“…A similar finding was observed with the clinically modified or adopted responder criteria (American Speech-Language-Hearing Association, 1994). This finding was comparable to the effect of ebselen on amikacin treated mice (Longenecker et al, 2020), and provides evidence that ebselen or other otoprotective drugs might work at ameliorating AG-induced hearing loss in clinic (Avci et al, 2016;Fox et al, 2016;Dogan et al, 2017;El-Anwar et al, 2018;Apaydin et al, 2021). However, the threshold shifts seen here were drastically different than those found with a similar tobramycin dosing experiment in Swiss-Webster mice (Gu et al, 2020).…”

Section: Tobramycin-induced Temporary Threshold Shifts Can Occur Without Permanent Cochlear Damagesupporting

confidence: 74%

Development of Tinnitus and Hyperacusis in a Mouse Model of Tobramycin Cochleotoxicity

Longenecker¹,

Gu²,

Homan³

et al. 2021

Front. Mol. Neurosci.

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Aminoglycosides (AG) antibiotics are a common treatment for recurrent infections in cystic fibrosis (CF) patients. AGs are highly ototoxic, resulting in a range of auditory dysfunctions. It was recently shown that the acoustic startle reflex (ASR) can assess behavioral evidence of hyperacusis and tinnitus in an amikacin cochleotoxicity mouse model. The goal of this study was to establish if tobramycin treatment led to similar changes in ASR behavior and to establish whether ebselen can prevent the development of these maladaptive neuroplastic symptoms. CBA/Ca mice were divided into three groups: Group 1 served as a control and did not receive tobramycin or ebselen, Group 2 received tobramycin (200 mg/kg/s.c.) and the vehicle (DMSO/saline/i.p.) daily for 14 continuous days, and Group 3 received the same dose/schedule of tobramycin as Group 2 and ebselen at (20 mg/kg/i.p.). Auditory brainstem response (ABR) and ASR hearing assessments were collected at baseline and 2, 6, 10, 14, and 18 weeks from the start of treatment. ASR tests included input/output (I/O) functions which assess general hearing and hyperacusis, and Gap-induced prepulse inhibition of the acoustic startle (GPIAS) to assess tinnitus. At 18 weeks, histologic analysis showed predominantly normal appearing hair cells and spiral ganglion neuron (SGN) synapses. Following 14 days of tobramycin injections, 16 kHz thresholds increased from baseline and fluctuated over the 18-week recovery period. I/O functions revealed exaggerated startle response magnitudes in 50% of mice over the same period. Gap detection deficits, representing behavioral evidence of tinnitus, were observed in a smaller subset (36%) of animals. Interestingly, increases in ABR wave III/wave I amplitude ratios were observed. These tobramycin data corroborate previous findings that AGs can result in hearing dysfunctions. We show that a 14-day course of tobramycin treatment can cause similar levels of hearing loss and tinnitus, when compared to a 14-day course of amikacin, but less hyperacusis. Evidence suggests that tinnitus and hyperacusis might be common side effects of AG antibiotics.

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Section: Tobramycin-induced Temporary Threshold Shifts Can Occur Without Permanent Cochlear Damagesupporting

confidence: 74%

Development of Tinnitus and Hyperacusis in a Mouse Model of Tobramycin Cochleotoxicity

Longenecker¹,

Gu²,

Homan³

et al. 2021

Front. Mol. Neurosci.

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“…With regard to ototoxicity due to aminoglycosides, many studies have been conducted on the anti-ototoxic effects of antioxidants. In animal studies, several antioxidants, such as NAC [137,138,139], D-methionine [140,141], edaravone [142], L-carnitine [143], pentoxifylline [144,145] and Q-ter [146], have been shown to reduce aminoglycoside-induced ototoxicity. Recently, a study using cochlea explant culture examined the preventive effect of a library of 81 antioxidants on HC damage induced by gentamycin [147].…”

Section: Mitochondria-targeted Antioxidants For Treatment Of Hearimentioning

confidence: 99%

Mitochondria-Targeted Antioxidants for Treatment of Hearing Loss: A Systematic Review

Fujimoto

Yamasoba

2019

Antioxidants

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Mitochondrial dysfunction is associated with the etiologies of sensorineural hearing loss, such as age-related hearing loss, noise- and ototoxic drug-induced hearing loss, as well as hearing loss due to mitochondrial gene mutation. Mitochondria are the main sources of reactive oxygen species (ROS) and ROS-induced oxidative stress is involved in cochlear damage. Moreover, the release of ROS causes further damage to mitochondrial components. Antioxidants are thought to counteract the deleterious effects of ROS and thus, may be effective for the treatment of oxidative stress-related diseases. The administration of mitochondria-targeted antioxidants is one of the drug delivery systems targeted to mitochondria. Mitochondria-targeted antioxidants are expected to help in the prevention and/or treatment of diseases associated with mitochondrial dysfunction. Of the various mitochondria-targeted antioxidants, the protective effects of MitoQ and SkQR1 against ototoxicity have been previously evaluated in animal models and/or mouse auditory cell lines. MitoQ protects against both gentamicin- and cisplatin-induced ototoxicity. SkQR1 also provides auditory protective effects against gentamicin-induced ototoxicity. On the other hand, decreasing effect of MitoQ on gentamicin-induced cell apoptosis in auditory cell lines has been controversial. No clinical studies have been reported for otoprotection using mitochondrial-targeted antioxidants. High-quality clinical trials are required to reveal the therapeutic effect of mitochondria-targeted antioxidants in terms of otoprotection in patients.

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“…Pentoxifylline is a hemorheologically active phosphodiesterase inhibitor that is a treatment option for sudden sensorineural hearing loss [8][9][10]. Recent data also suggest that pentoxifylline protects the inner ear from amikacin-induced ototoxicity [11]. Moreover, pentoxifylline has been put forward as a neuroprotective and trophic agent that improves the viability of striatal neurons in an animal model of Parkinson's disease [12] and stimulates the sprouting of neuronal processes from cultured pelvic ganglia [13].…”

Section: Introductionmentioning

confidence: 99%

Simultaneous treatment with pentoxifylline does not adversely affect the neurotrophic effects of brain-derived neurotrophic factor on spiral ganglion neurons

Geißler¹,

Blumenstock²,

Gabrielpillai³

et al. 2021

NeuroReport

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The hemorheologic drug pentoxifylline is applied for the treatment of sudden sensorineural hearing loss and tinnitus to improve cochlear microcirculation. Recent studies also suggest protective and trophic effects on neuronal cells. Because the preservation of sensorineural structures of the inner ear is fundamental for normal hearing and hearing restoration with auditory prostheses, pentoxifylline and neurotrophic factors such as brain-derived neurotrophic factor (BDNF) are promising candidates to treat degenerative disorders of the inner ear. We used an in-vitro model to determine the neurotrophic effects of these factors on spiral ganglion cells from postnatal rats. Pentoxifylline, alone and in combination with BDNF, was added at various concentrations to the cultured cells. Cells were immunolabeled and analyzed to determine neuronal survival, neurite length, neuronal branching and morphology. Pentoxifylline did not significantly increase or decrease neuronal survival, neurite length and neuronal branching compared to control cultures. Analysis of cellular morphology showed that diverse neuronal subtypes developed in the presence of pentoxifylline. Our data revealed that pentoxifylline did not interfere with the robust neurotrophic effects of BDNF on spiral ganglion neurons when cultured cells were treated with pentoxifylline and BDNF simultaneously. The results of our study do not suggest major neurotrophic effects of pentoxifylline on cultured spiral ganglion neurons. Because pentoxifylline has no detrimental effects on spiral ganglion neurons and does not reduce the effects of BDNF, both agents could be combined to treat diseases of the inner ear provided that future in vivo experiments and clinical studies support these findings.

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Protective Effect of Pentoxifylline on Amikacin-Induced Ototoxicity

Cited by 4 publications

References 20 publications

Development of Tinnitus and Hyperacusis in a Mouse Model of Tobramycin Cochleotoxicity

Development of Tinnitus and Hyperacusis in a Mouse Model of Tobramycin Cochleotoxicity

Mitochondria-Targeted Antioxidants for Treatment of Hearing Loss: A Systematic Review

Simultaneous treatment with pentoxifylline does not adversely affect the neurotrophic effects of brain-derived neurotrophic factor on spiral ganglion neurons

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