Berbamine Analogs Exhibit Differential Protective Effects From Aminoglycoside-Induced Hair Cell Death.
Hearing loss is the third most common chronic health condition in the United States and largely results from damage to sensory hair cells. Major causes of hair cell damage include aging, noise exposure, and medications such as aminoglycoside antibiotics. Due to their potent antibacterial properties and low cost, aminoglycosides are often used for the treatment of gram-negative bacterial infections, surpassing expensive antibiotics with fewer harmful side effects. However, their use is coupled with permanent hearing loss in over 20% of patients requiring these life-sustaining antibiotics. There are currently no FDA-approved drugs that prevent hearing loss from aminoglycosides. A previous study by our group identified the plant alkaloid berbamine as a strong protectant of zebrafish lateral line hair cells from aminoglycoside damage. This effect is likely due to a block of the mechanotransduction channel, thereby reducing aminoglycoside entry into hair cells. The present study builds on this previous work, investigating 16 synthetic berbamine analogs to determine the core structure underlying their protective mechanisms. We demonstrate that nearly all of these berbamine analogs robustly protect lateral line hair cells from ototoxic damage, with ED
Published In/Presented At
Hudson, A. M., Lockard, G. M., Namjoshi, O. A., Wilson, J. W., Kindt, K. S., Blough, B. E., & Coffin, A. B. (2020). Berbamine Analogs Exhibit Differential Protective Effects From Aminoglycoside-Induced Hair Cell Death. Frontiers in cellular neuroscience, 14, 234. https://doi.org/10.3389/fncel.2020.00234
Medical Education | Medicine and Health Sciences
USF-LVHN SELECT Program, USF-LVHN SELECT Program Students