Natural compounds protect Zebrafish lateral line sensory hair cells from Aminoglycoside toxicity

Matthew Wayne Kruger

Moderate to severe hearing loss affects 360 million people worldwide. In the US alone, hearing loss affects nearly 37.5 million people, resulting in a loss in household income of nearly $20,000 a year. Hearing results when sensory hair cells in our inner ear transduce auditory stimuli into electrochemical signals that are sent to our brain for processing. These cells can be damaged as a result of aging, genetics, excess noise exposure, and some medications, resulting in permanent hearing loss. Aminoglycoside antibiotics are effective at treating infections such as those associated with cystic fibrosis and sepsis, yet these antibiotics cause hearing loss in 20-30% of patients. Therefore, discovering compounds that prevent aminoglycoside-induced hair cell death will prevent a devastating side effect of these life-saving antibiotics. Plant derived natural compounds have been used in eastern medicine for thousands of years and are widely used as a source of new drugs for cancer and other diseases. Therefore, natural compounds provide a novel source of potential hair cell protective compounds. Here we use the larval zebrafish lateral line as a model to screen for natural compounds that protect hair cells from aminoglycoside-induced damage. Zebrafish hair cells are structurally and functionally similar to mammalian inner ear hair cells and respond similarly to toxins, making it likely that compounds discovered with zebrafish will protect mammalian hair cells. We discovered four natural compounds, berbamine (ber), e6 berbamine (e6), hernandezine (her), and isotetrandrine (iso), that robustly protected hair cells from aminoglycoside-induced hair cell damage by reducing uptake of the toxin into hair cells. Ber, e6, and iso did not interfere with antibiotic efficacy. Furthermore, e6 did not significantly reduce hair cell function. Future experiments are needed to determine if these natural compounds protect mammalian hair cells. Ber, e6, and iso collectively represent a novel source of potential otoprotective drugs that could progress to clinical trials, offering therapeutic options for patients taking these lifesaving antibiotics.

Natural compounds protect Zebrafish lateral line sensory hair cells from Aminoglycoside toxicity

Files and links (1)

Abstract

Metrics

Details