Effects of Androgen Receptor Inhibition on Kanamycin-Induced Hearing Loss in Rats

Chun, Kyung-Ju; Lee, Chang-Ho; Kim, Kyung-Woon; Lee, So-Min; Kim, Soyoung

doi:10.3390/ijms22105307

Cited by 8 publications

(4 citation statements)

References 31 publications

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“…As a result, whether androgen plays an essential role in ASNHL is still unclear. One recent report revealed that AR inhibition protected against cochlear injuries in kanamycin-induced hearing loss in rats [ 134 ]. Further investigations are needed to elucidate the role of androgen in the auditory system.…”

Section: How Could Hormones Influence Hearing In Molecular Aspects?mentioning

confidence: 99%

Sex Differences in the Triad of Acquired Sensorineural Hearing Loss

Lien

Yang

2021

IJMS

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The triad of noise-generated, drug-induced, and age-related hearing loss is the major cause of acquired sensorineural hearing loss (ASNHL) in modern society. Although these three forms of hearing loss display similar underlying mechanisms, detailed studies have revealed the presence of sex differences in the auditory system both in human and animal models of ASNHL. However, the sexual dimorphism of hearing varies among noise-induced hearing loss (NIHL), ototoxicity, and age-related hearing loss (ARHL). Importantly, estrogen may play an essential role in modulating the pathophysiological mechanisms in the cochlea and several reports have shown that the effects of hormone replacement therapy on hearing loss are complex. This review will summarize the clinical features of sex differences in ASNHL, compare the animal investigations of cochlear sexual dimorphism in response to the three insults, and address how estrogen affects the auditory organ at molecular levels.

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Section: How Could Hormones Influence Hearing In Molecular Aspects?mentioning

confidence: 99%

Sex Differences in the Triad of Acquired Sensorineural Hearing Loss

Lien

Yang

2021

IJMS

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“…Current research has confirmed that CYP1B1 can affect the ubiquitination regulation of ACSL4 in the process of ferroptosis 13 . Additionally, reports have shown that high expression of CYP1B1 could improve brain injury 23–25 . Therefore, we further investigated the expression of CYP1B1 in brain tissue following melatonin treatment and observed a significant increase in CYP1B1 expression, accompanied by a notable decrease in ACSL4 expression.…”

Section: Discussionmentioning

confidence: 76%

“…13 Additionally, reports have shown that high expression of CYP1B1 could improve brain injury. [23][24][25] Therefore, we further investigated the…”

Section: Discussionmentioning

confidence: 99%

Melatonin alleviates ischemic stroke by inhibiting ferroptosis through the CYP1B1/ACSL4 pathway

Sun,

Jin,

et al. 2024

Environmental Toxicology

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This study utilized middle cerebral artery occlusion (MCAO) mouse models and HT‐22 cell oxygen and glucose deprivation/reoxygenation (OGD/R) models to investigate the therapeutic effects of melatonin on ischemic brain injury. In the experiments, MCAO mice were treated with 5 and 10 mg/kg doses of melatonin, and H‐T22 cells underwent OGD/R treatment and were administered different concentrations of melatonin. The results showed that melatonin significantly reduced ischemic brain area, neural damage, cerebral edema, and neuronal apoptosis in MCAO mice. In the HT‐22 cell model, melatonin also improved cell proliferation ability, reduced apoptosis, and ROS production. Further mechanistic studies found that melatonin exerts protective effects by inhibiting ferroptosis, an iron‐dependent form of regulated cell death, through regulation of the ACSL4/CYP1B1 pathway. In MCAO mice, melatonin decreased lipid peroxidation, ROS production, and ACSL4 protein expression. Overexpression of CYP1B1 increased ACSL4 ubiquitination and degradation, thereby increasing cell tolerance to ferroptosis, reducing ACSL4 protein levels, and decreasing ROS production. CYP1B1 knockdown obtained opposite results. The CYP1B1 metabolite 20‐HETE induces expression of the E3 ubiquitin ligase FBXO10 by activating PKC signaling, which promotes ACSL4 degradation. In the OGD/R cell model, inhibition of CYP1B1 expression reversed the therapeutic effects of melatonin. In summary, this study demonstrates that melatonin protects the brain from ischemic injury by inhibiting ferroptosis through regulation of the ACSL4/CYP1B1 pathway, providing evidence for new therapeutic targets for ischemic brain injury.

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“…Aminoglycosides induce high calcium uptake by mitochondria in cochlear hair cells, which results in the secretion of pro-apoptotic factors and oxidative enzymes into the cytoplasm and generates reactive oxidative species [ 15 ]. The attenuation of oxidative stress and inflammatory responses was reported to have a protective effect on aminoglycoside-inducted ototoxicity [ 16 ]. Therefore, TM was presumed to have a protective effect on aminoglycoside-induced hearing loss.…”

Section: Introductionmentioning

confidence: 99%

Telmisartan Attenuates Kanamycin-Induced Ototoxicity in Rats

Lee

Kim

2021

IJMS

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Telmisartan (TM) has been proposed to relieve inflammatory responses by modulating peroxisome proliferator activator receptor-γ (PPARγ) signaling. This study aimed to investigate the protective effects of TM on kanamycin(KM)-induced ototoxicity in rats. Forty-eight, 8-week-old female Sprague Dawley rats were divided into four groups: (1) control group, (2) TM group, (3) KM group, and (4) TM + KM group. Auditory brainstem response was measured. The histology of the cochlea was examined. The protein expression levels of angiotensin-converting enzyme 2 (ACE2), HO1, and PPARγ were measured by Western blotting. The auditory threshold shifts at 4, 8, 16, and 32 kHz were lower in the TM + KM group than in the KM group (all p < 0.05). The loss of cochlear outer hair cells and spiral ganglial cells was lower in the TM + KM group than in the KM group. The protein expression levels of ACE2, PPARγ, and HO1 were higher in the KM group than in the control group (all p < 0.05). The TM + KM group showed lower expression levels of PPARγ and HO1 than the KM group.TM protected the cochlea from KM-induced injuries in rats. TM preserved hearing levels and attenuated the increase in PPARγ and HO1 expression levels in KM-exposed rat cochleae.

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Effects of Androgen Receptor Inhibition on Kanamycin-Induced Hearing Loss in Rats

Cited by 8 publications

References 31 publications

Sex Differences in the Triad of Acquired Sensorineural Hearing Loss

Sex Differences in the Triad of Acquired Sensorineural Hearing Loss

Melatonin alleviates ischemic stroke by inhibiting ferroptosis through the CYP1B1/ACSL4 pathway

Telmisartan Attenuates Kanamycin-Induced Ototoxicity in Rats

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