ArticleScience translational medicine2024
Piplartine attenuates aminoglycoside-induced TRPV1 activity and protects from hearing loss in mice.
Article in Science translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- TRPV4 mediates aminoglycoside trafficking and ototoxicity without compromising antimicrobial efficacy.Cell death discovery · 2026Article
- Pharmacologic Inhibition of JAK1/2 Potentiates Aminoglycoside-Induced Ototoxicity.Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology · 2026Article
- Effects of Methionine and Glutathione on Acute Ototoxicity Induced by Amikacin and Furosemide in an Animal Model of Hearing Threshold Decrease.Biomedicines · 2025Article
- TRP channels in mammalian hearing loss.Frontiers in molecular neuroscience · 2025Review
- Paving the way for better ototoxicity assessments in cisplatin therapy using more reliable animal models.Frontiers in cellular neuroscience · 2025Article
- Mechanistic insights into cisplatin-induced ototoxicity: the central role of transient receptor potential channels.Frontiers in molecular biosciences · 2025Review
- Age-related hearing loss in older adults: etiology and rehabilitation strategies.Frontiers in neuroscience · 2024Review
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Authors and funding
16 authors.
Funding
Abstract
Hearing loss is a major health concern in our society, affecting more than 400 million people worldwide. Among the causes, aminoglycoside therapy can result in permanent hearing loss in 40% to 60% of patients receiving treatment, and despite these high numbers, no drug for preventing or treating this type of hearing loss has yet been approved by the US Food and Drug Administration. We have previously conducted high-throughput screenings of bioactive compounds, using zebrafish as our discovery platform, and identified piplartine as a potential therapeutic molecule. In the present study, we expanded this work and characterized piplartine's physicochemical and therapeutic properties. We showed that piplartine had a wide therapeutic window and neither induced nephrotoxicity in vivo in zebrafish nor interfered with aminoglycoside antibacterial activity. In addition, a fluorescence-based assay demonstrated that piplartine did not inhibit cytochrome C activity in microsomes. Coadministration of piplartine protected from kanamycin-induced hair cell loss in zebrafish and protected hearing function, outer hair cells, and presynaptic ribbons in a mouse model of kanamycin ototoxicity. Last, we investigated piplartine's mechanism of action by phospho-omics, immunoblotting, immunohistochemistry, and molecular dynamics experiments. We found an up-regulation of AKT1 signaling in the cochleas of mice cotreated with piplartine. Piplartine treatment normalized kanamycin-induced up-regulation of TRPV1 expression and modulated the gating properties of this receptor. Because aminoglycoside entrance to the inner ear is, in part, mediated by TRPV1, these results suggested that by regulating TRPV1 expression, piplartine blocked aminoglycoside's entrance, thereby preventing the long-term deleterious effects of aminoglycoside accumulation in the inner ear compartment.
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