Protective Effects of (-)-Butaclamol Against Gentamicin-Induced Ototoxicity: In Vivo and In Vitro Approaches

Area of Science:

• Ototoxicity research
• Drug discovery
• Cellular biology

Background:

• Gentamicin antibiotic can cause irreversible hearing loss by damaging inner ear hair cells.
• Identifying protective agents is crucial for preventing gentamicin-induced ototoxicity.

Purpose of the Study:

• To identify a potent protective agent against gentamicin-induced ototoxicity.
• To elucidate the protective mechanisms of the identified compound.

Main Methods:

• High-content screening (HCS) of a natural compound library.
• Cell viability assays in HEI-OC1 cells and zebrafish neuromasts.
• Apoptosis markers (TUNEL, BAX, caspase-3, BCL-2), signaling pathways (AKT/mTOR, ERK, NF-κB), oxidative stress (CellROX), autophagy (LysoTracker), and mitochondrial potential (TMRE) were analyzed.

Main Results:

• (-)-Butaclamol was identified as a potent protective agent against gentamicin cytotoxicity.
• (-)-Butaclamol enhanced cell viability, inhibited apoptosis, and reduced oxidative stress.
• The compound activated survival pathways (AKT/mTOR, ERK), suppressed inflammation (NF-κB), restored autophagy, and preserved mitochondrial function.

Conclusions:

• (-)-Butaclamol offers comprehensive cytoprotection against gentamicin-induced ototoxicity.
• Mechanisms include apoptosis inhibition, survival pathway activation, and restoration of cellular homeostasis.
• (-)-Butaclamol shows significant therapeutic potential for preventing hearing loss.