PUBLICATION
Naringin attenuates cisplatin- and aminoglycoside-induced hair cell injury in the zebrafish lateral line via multiple pathways
- Authors
- Li, M., Liu, J., Liu, D., Duan, X., Zhang, Q., Wang, D., Zheng, Q., Bai, X., Lu, Z.
- ID
- ZDB-PUB-201208-27
- Date
- 2020
- Source
- Journal of Cellular and Molecular Medicine 25(2): 975-989 (Journal)
- Registered Authors
- Keywords
- aminoglycosides, cisplatin, naringin, ototoxicity, therapeutic
- MeSH Terms
-
- Aminoglycosides/adverse effects*
- Animals
- Cell Death/drug effects
- Cell Proliferation/drug effects
- Cilia/drug effects
- Cilia/metabolism
- Cilia/pathology
- Cisplatin/adverse effects*
- Flavanones/pharmacology*
- Gentamicins/adverse effects
- Hair Cells, Auditory/drug effects
- Hair Cells, Auditory/pathology*
- Lateral Line System/drug effects
- Lateral Line System/pathology*
- Mitochondria/drug effects
- Mitochondria/metabolism
- Neomycin/toxicity
- Oxidative Stress/drug effects
- Protective Agents/pharmacology
- Pyroptosis/drug effects
- Pyroptosis/genetics
- Reactive Oxygen Species/metabolism
- Regeneration/drug effects
- Signal Transduction*/drug effects
- Toxicity Tests, Acute
- Zebrafish
- PubMed
- 33274582 Full text @ J. Cell. Mol. Med.
Citation
Li, M., Liu, J., Liu, D., Duan, X., Zhang, Q., Wang, D., Zheng, Q., Bai, X., Lu, Z. (2020) Naringin attenuates cisplatin- and aminoglycoside-induced hair cell injury in the zebrafish lateral line via multiple pathways. Journal of Cellular and Molecular Medicine. 25(2):975-989.
Abstract
Exposure to ototoxic drugs is a significant cause of hearing loss that affects about 30 thousand children with potentially serious physical, social and psychological dysfunctions every year. Cisplatin (CP) and aminoglycosides are effective antineoplastic or bactericidal drugs, and their application has a high probability of ototoxicity which results from the death of hair cells (HCs). Here, we describe the therapeutic effect of the flavonoid compound naringin (Nar) against ototoxic effects of cisplatin and aminoglycosides include gentamicin (GM) and neomycin (Neo) in zebrafish HCs. Animals incubated with Nar (100-400 μmol/L) were protected against the pernicious effects of CP (150-250 μmol/L), GM (50-150 μmol/L) and Neo (50-150 μmol/L). We also provide evidence for the potential mechanism of Nar against ototoxicity, including antioxidation, anti-apoptosis, promoting proliferation and hair cell regeneration. We found that mRNA levels of the apoptotic- and pyroptosis-related genes are regulated by Nar both in vivo and in vitro. Finally, by proving that Nar does not affect the anti-tumour efficacy of CP and antibacterial activity of aminoglycosides in vitro, we highlight its value in clinical application. In conclusion, these results unravel a novel therapeutic role for Nar as an otoprotective drug against the adverse effects of CP and aminoglycosides.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping