Evaluation of Mitoquinone for Protecting Against Amikacin-Induced Ototoxicity in Guinea Pigs

Dirain, Carolyn O.; Ng, Maria Raye Ann V.; Milne-Davies, Bailey; Joseph, Jerin; Antonelli, Patrick J.

doi:10.1097/mao.0000000000001638

Cited by 14 publications

(9 citation statements)

References 36 publications

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“…Moreover, two previous in vivo studies found protective effects of MitoQ in the inner ear. Using gentamicin- or amikacin-treated guinea pigs, it was shown that the administration of MitoQ attenuated aminoglycoside-induced ototoxicity, leading to cochlear damage and hypoacusia [44] , [45] . Although the protective effect of MitoQ against ototoxicity was determined in previous studies, an important significance of this study is the suggestion of the possibility to reverse genetic hearing loss.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic potential of the mitochondria-targeted antioxidant MitoQ in mitochondrial-ROS induced sensorineural hearing loss caused by Idh2 deficiency

et al. 2019

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Mitochondrial NADP+-dependent isocitrate dehydrogenase 2 (IDH2) is a major NADPH-producing enzyme which is essential for maintaining the mitochondrial redox balance in cells. We sought to determine whether IDH2 deficiency induces mitochondrial dysfunction and modulates auditory function, and investigated the protective potential of an antioxidant agent against reactive oxygen species (ROS)-induced cochlear damage in Idh2 knockout (Idh2−/−) mice. Idh2 deficiency leads to damages to hair cells and spiral ganglion neurons (SGNs) in the cochlea and ultimately to apoptotic cell death and progressive sensorineural hearing loss in Idh2−/− mice. Loss of IDH2 activity led to decreased levels of NADPH and glutathione causing abnormal ROS accumulation and oxidative damage, which might trigger apoptosis signal in hair cells and SGNs in Idh2−/− mice. We performed ex vivo experiments to determine whether administration of mitochondria-targeted antioxidants might protect or induce recovery of cells from ROS-induced apoptosis in Idh2-deficient mouse cochlea. MitoQ almost completely neutralized the H2O2-induced ototoxicity, as the survival rate of Idh2−/− hair cells were restored to normal levels. In addition, the lack of IDH2 led to the accumulation of mitochondrial ROS and the depolarization of ΔΨm, resulting in hair cell loss. In the present study, we identified that IDH2 is indispensable for the functional maintenance and survival of hair cells and SGNs. Moreover, the hair cell degeneration caused by IDH2 deficiency can be prevented by MitoQ, which suggests that Idh2−/− mice could be a valuable animal model for evaluating the therapeutic effects of various antioxidant candidates to overcome ROS-induced hearing loss.

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Section: Discussionmentioning

confidence: 99%

Therapeutic potential of the mitochondria-targeted antioxidant MitoQ in mitochondrial-ROS induced sensorineural hearing loss caused by Idh2 deficiency

et al. 2019

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“…We screened all 20 identified records and removed all studies that were not relevant to the subject matter. The remaining 8 records were summarized in this section [9,10,11,12,13,14,15,16]. Among the mitochondria-targeted antioxidants, MitoQ and SkQR1 have been used for studying the treatment of SNHL (Table 1).…”

Section: Mitochondria-targeted Antioxidants For Treatment Of Hearimentioning

confidence: 99%

“…There have been several reports using MitoQ and SkQR1 to demonstrate the protective effect of mitochondria-targeted antioxidants against ototoxicity in animal models and/or mouse auditory cell lines [9,10,11,12,13,14,15,16]. Oral MitoQ treatment reduced gentamicin-induced cochlear damage and hearing loss in guinea pigs [15].…”

Section: Mitochondria-targeted Antioxidants For Treatment Of Hearimentioning

confidence: 99%

“…In HEI-OC1 cells, co-incubation with low-dose gentamicin and MitoQ decreased mitochondrial membrane potential, whereas co-incubation with high-dose gentamicin and MitoQ hyperpolarized the mitochondrial membrane, suggesting that the combination of gentamicin and MitoQ has the potential to disrupt the mitochondrial membrane [13]. Oral or transcutaneous MitoQ administration provided limited protection against amikacin-induced hearing loss and cochlear damage in guinea pigs [9]. Subcutaneous MitoQ administration significantly reduced cisplatin-induced OHC loss and hearing loss in guinea pigs [16].…”

Section: Mitochondria-targeted Antioxidants For Treatment Of Hearimentioning

confidence: 99%

“…Mitochondria-targeted antioxidants are superior in attenuating mitochondrial oxidative damage [6,7,8]. There has also been research focusing on the application of these mitochondria-targeted antioxidants in the treatment of hearing loss [9,10,11,12,13,14,15,16].…”

Section: Introductionmentioning

confidence: 99%

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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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The Role and Research Progress of Mitochondria in Sensorineural Hearing Loss

Xu,

Yang

2024

Mol Neurobiol

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Evaluation of Mitoquinone for Protecting Against Amikacin-Induced Ototoxicity in Guinea Pigs

Abstract: Oral or subcutaneous MitoQ provided limited protection against amikacin-induced hearing loss and cochlear damage in guinea pigs. Other strategies for attenuating aminoglycoside-induced ototoxicity should be explored.

Cited by 14 publications

References 36 publications

Therapeutic potential of the mitochondria-targeted antioxidant MitoQ in mitochondrial-ROS induced sensorineural hearing loss caused by Idh2 deficiency

Therapeutic potential of the mitochondria-targeted antioxidant MitoQ in mitochondrial-ROS induced sensorineural hearing loss caused by Idh2 deficiency

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

The Role and Research Progress of Mitochondria in Sensorineural Hearing Loss

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