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Protective Effects of (-)-Butaclamol Against Gentamicin-Induced Ototoxicity: In Vivo and In Vitro Approaches
by
Rah, Yoon Chan
, Kim, Hwee-Jin
, Han, Eunjung
, Baek, Hyun woo
, Hyun, Kyungtae
, Choi, June
, Park, Saemi
, Hong, Sumin
, Lee, Yunkyoung
in
Aminoglycosides
/ Analysis
/ Animals
/ Antipsychotics
/ Apoptosis
/ Apoptosis - drug effects
/ Autophagy - drug effects
/ Cell death
/ Cell Line
/ Cell Survival - drug effects
/ Cytotoxicity
/ Dopamine
/ Gentamicins - adverse effects
/ Gentamicins - toxicity
/ Hair Cells, Auditory - drug effects
/ Hearing loss
/ Hearing protection
/ Humans
/ Membrane Potential, Mitochondrial - drug effects
/ Ototoxicity - drug therapy
/ Ototoxicity - etiology
/ Ototoxicity - metabolism
/ Ototoxicity - pathology
/ Ototoxicity - prevention & control
/ Oxidative Stress - drug effects
/ Protective Agents - pharmacology
/ Proteins
/ Psychotropic drugs
/ Signal Transduction - drug effects
/ Somatotropin
/ Toxicity
/ Zebrafish
2025
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Protective Effects of (-)-Butaclamol Against Gentamicin-Induced Ototoxicity: In Vivo and In Vitro Approaches
by
Rah, Yoon Chan
, Kim, Hwee-Jin
, Han, Eunjung
, Baek, Hyun woo
, Hyun, Kyungtae
, Choi, June
, Park, Saemi
, Hong, Sumin
, Lee, Yunkyoung
in
Aminoglycosides
/ Analysis
/ Animals
/ Antipsychotics
/ Apoptosis
/ Apoptosis - drug effects
/ Autophagy - drug effects
/ Cell death
/ Cell Line
/ Cell Survival - drug effects
/ Cytotoxicity
/ Dopamine
/ Gentamicins - adverse effects
/ Gentamicins - toxicity
/ Hair Cells, Auditory - drug effects
/ Hearing loss
/ Hearing protection
/ Humans
/ Membrane Potential, Mitochondrial - drug effects
/ Ototoxicity - drug therapy
/ Ototoxicity - etiology
/ Ototoxicity - metabolism
/ Ototoxicity - pathology
/ Ototoxicity - prevention & control
/ Oxidative Stress - drug effects
/ Protective Agents - pharmacology
/ Proteins
/ Psychotropic drugs
/ Signal Transduction - drug effects
/ Somatotropin
/ Toxicity
/ Zebrafish
2025
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Protective Effects of (-)-Butaclamol Against Gentamicin-Induced Ototoxicity: In Vivo and In Vitro Approaches
by
Rah, Yoon Chan
, Kim, Hwee-Jin
, Han, Eunjung
, Baek, Hyun woo
, Hyun, Kyungtae
, Choi, June
, Park, Saemi
, Hong, Sumin
, Lee, Yunkyoung
in
Aminoglycosides
/ Analysis
/ Animals
/ Antipsychotics
/ Apoptosis
/ Apoptosis - drug effects
/ Autophagy - drug effects
/ Cell death
/ Cell Line
/ Cell Survival - drug effects
/ Cytotoxicity
/ Dopamine
/ Gentamicins - adverse effects
/ Gentamicins - toxicity
/ Hair Cells, Auditory - drug effects
/ Hearing loss
/ Hearing protection
/ Humans
/ Membrane Potential, Mitochondrial - drug effects
/ Ototoxicity - drug therapy
/ Ototoxicity - etiology
/ Ototoxicity - metabolism
/ Ototoxicity - pathology
/ Ototoxicity - prevention & control
/ Oxidative Stress - drug effects
/ Protective Agents - pharmacology
/ Proteins
/ Psychotropic drugs
/ Signal Transduction - drug effects
/ Somatotropin
/ Toxicity
/ Zebrafish
2025
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Protective Effects of (-)-Butaclamol Against Gentamicin-Induced Ototoxicity: In Vivo and In Vitro Approaches
Journal Article
Protective Effects of (-)-Butaclamol Against Gentamicin-Induced Ototoxicity: In Vivo and In Vitro Approaches
2025
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Overview
Gentamicin-induced ototoxicity leads to irreversible sensorineural hearing loss due to structural and functional damage to inner ear hair cells. In this study, we identified (-)-butaclamol as a potent protective agent against gentamicin-induced cytotoxicity through high-content screening (HCS) of a natural compound library. (-)-Butaclamol significantly enhanced cell viability in both HEI-OC1 cells and zebrafish neuromasts, demonstrating robust protection against gentamicin toxicity. Mechanistically, (-)-butaclamol inhibited intrinsic apoptosis, as evidenced by reduced TUNEL-positive cell counts and the downregulation of BAX and caspase-3, alongside the upregulation of BCL-2. Moreover, (-)-butaclamol activated key survival signaling pathways, including AKT/mTOR and ERK, while suppressing the inflammatory regulator NF-κB. Additional analyses revealed that (-)-butaclamol effectively mitigated oxidative stress and restored autophagic activity, as confirmed by CellROX and LysoTracker assays. Notably, TMRE staining showed that (-)-butaclamol preserved mitochondrial membrane potential in zebrafish hair cells, indicating mitochondrial protection. Collectively, these findings suggest that (-)-butaclamol exerts comprehensive cytoprotective effects against gentamicin-induced ototoxicity by modulating apoptosis, enhancing survival signaling, and restoring mitochondrial and cellular homeostasis. These results highlight the therapeutic potential of (-)-butaclamol and provide a foundation for future studies aimed at its clinical application.
Publisher
MDPI AG,MDPI
Subject
/ Analysis
/ Animals
/ Cell Survival - drug effects
/ Dopamine
/ Gentamicins - adverse effects
/ Hair Cells, Auditory - drug effects
/ Humans
/ Membrane Potential, Mitochondrial - drug effects
/ Ototoxicity - prevention & control
/ Oxidative Stress - drug effects
/ Protective Agents - pharmacology
/ Proteins
/ Signal Transduction - drug effects
/ Toxicity
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