PUBLICATION

Natural Compounds as Occult Ototoxins? Ginkgo biloba Flavonoids Moderately Damage Lateral Line Hair Cells

Authors
Neveux, S., Smith, N.K., Roche, A., Blough, B.E., Pathmasiri, W., Coffin, A.B.
ID
ZDB-PUB-161130-4
Date
2017
Source
Journal of the Association for Research in Otolaryngology : JARO   18(2): 275-289 (Journal)
Registered Authors
Coffin, Allison
Keywords
Hearing loss, Herbal supplements, Oxidative stress, Zebrafish
MeSH Terms
  • Animals
  • Calcium Signaling
  • Ginkgo biloba
  • Hair Cells, Auditory/drug effects*
  • Kaempferols/toxicity*
  • Plant Extracts/toxicity*
  • Quercetin/analogs & derivatives
  • Quercetin/toxicity*
  • Zebrafish
PubMed
27896487 Full text @ J. Assoc. Res. Otolaryngol.
Abstract
Several drugs, including aminoglycosides and platinum-based chemotherapy agents, are well known for their ototoxic properties. However, FDA-approved drugs are not routinely tested for ototoxicity, so their potential to affect hearing often goes unrecognized. This issue is further compounded for natural products, where there is a lack of FDA oversight and the manufacturer is solely responsible for ensuring the safety of their products. Natural products such as herbal supplements are easily accessible and commonly used in the practice of traditional eastern and alternative medicine. Using the zebrafish lateral line, we screened a natural products library to identify potential ototoxins. We found that the flavonoids quercetin and kaempferol, both from the Gingko biloba plant, demonstrated significant ototoxicity, killing up to 30 % of lateral line hair cells. We then examined a third Ginkgo flavonoid, isorhamnetin, and found similar levels of ototoxicity. After flavonoid treatment, surviving hair cells demonstrated reduced uptake of the vital dye FM 1-43FX, suggesting that the health of the remaining hair cells was compromised. We then asked if these flavonoids enter hair cells through the mechanotransduction channel, which is the site of entry for many known ototoxins. High extracellular calcium or the quinoline derivative E6 berbamine significantly protected hair cells from flavonoid damage, implicating the transduction channel as a site of flavonoid uptake. Since known ototoxins activate cellular stress responses, we asked if reactive oxygen species were necessary for flavonoid ototoxicity. Co-treatment with the antioxidant D-methionine significantly protected hair cells from each flavonoid, suggesting that antioxidant therapy could prevent hair cell loss. How these products affect mammalian hair cells is still an open question and will be the target of future experiments. However, this research demonstrates the potential for ototoxic damage caused by unregulated herbal supplements and suggests that further supplement characterization is warranted.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping