ArticleCell death & disease2019
Pasireotide protects mammalian cochlear hair cells from gentamicin ototoxicity by activating the PI3K-Akt pathway.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- Multi-scale analysis reveals key targets mediating BPA-induced sensorineural hearing loss.Medicine · 2026Article
- Human induced pluripotent stem cell-derived inner ear organoids reveal hair cell damage and plasticity after cisplatin and gentamicin exposure.Disease models & mechanisms · 2026Article
- Therapeutic Potential of Somatostatin and Its Analogues in Alzheimer's Disease: From Molecular Mechanisms to Preclinical Studies.Molecular neurobiology · 2026Review
- Experimental and Clinical Approaches to Preventing Aminoglycoside-Induced Ototoxicity: A Scoping Review.Antioxidants (Basel, Switzerland) · 2025Review
- Comparative Cochlear Transcriptomics in Echolocating Bats and Mouse Reveals Hras as Protector Against Noise-Induced Hearing Loss.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Protective Effects of Pasireotide in LPS-Induced Acute Lung Injury.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Exploring the bioactive ingredients of three traditional Chinese medicine formulas against age-related hearing loss through network pharmacology and experimental validation.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- The Upregulation of IL-1β Induced by Cisplatin Triggers PI3K/AKT/MMP9 Pathway in Pericytes Mediating the Leakage of the Blood Labyrinth Barrier.Journal of inflammation research · 2025Article
- Studies on the mechanism of ototoxic action of cisplatin and the antagonistic effect of polyphenolic compounds.Frontiers in pharmacology · 2025Review
- Ivacaftor attenuates gentamicin-induced ototoxicity through the CFTR-Nrf2-HO1/NQO1 pathway.Redox report : communications in free radical research · 2024Article
- Article
- Environmental pollutants and phosphoinositide signaling in autoimmunity.Journal of hazardous materials · 2024Review
- Extracellular vesicles for developing targeted hearing loss therapy.Journal of controlled release : official journal of the Controlled Release Society · 2024Review
- Formononetin ameliorates cisplatin-induced hair cell death via activation of the PI3K/AKT-Nrf2 signaling pathway.Heliyon · 2024Article
- PTEN inhibitor bisperoxovanadium protects against noise-induced hearing loss.Neural regeneration research · 2023Article
- Network pharmacology and experimental evidence reveal the protective mechanism of Yi-Qi Cong-Ming decoction on age-related hearing loss.Pharmaceutical biology · 2022Article
- Inhibiting DNA methylation alleviates cisplatin-induced hearing loss by decreasing oxidative stress-induced mitochondria-dependent apoptosisActa pharmaceutica Sinica. B · 2022Article
- c-Myb protects cochlear hair cells from cisplatin-induced damage via the PI3K/Akt signaling pathway.Cell death discovery · 2022Article
- Interference with megalin expression/endocytic function by montelukast mitigates gentamicin nephrotoxicity: Downregulation of ClC-5 expression.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Article
- Key Signaling Pathways Regulate the Development and Survival of Auditory Hair Cells.Neural plasticity · 2021Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gentamicin is a widely used antibiotic for the treatment of gram-negative bacterial infections; however, its use often results in significant and permanent hearing loss. Hearing loss resulting from hair cell (HC) degeneration affects millions of people worldwide, and one major cause is the loss of sensory HCs in the inner ear due to aminoglycoside exposure. Strategies to overcome the apparently irreversible loss of HCs in mammals are crucial for hearing protection. Here, we report that the somatostatin analog pasireotide protects mouse cochlear HCs from gentamicin damage using a well-established in vitro gentamicin-induced HC loss model and that the otoprotective effects of pasireotide are due to Akt up-regulation via the PI3K-Akt signal pathway activation. We demonstrate active caspase signal in organ of Corti (OC) explants exposed to gentamicin and show that pasireotide treatment activates survival genes, reduces caspase signal, and increases HC survival. The neuropeptide somatostatin and its selective analogs have provided neuroprotection by activating five somatostatin receptor (SSTR1-SSTR5) subtypes. Pasireotide has a high affinity for SSTR2 and SSTR5, and the addition of SSTR2- and SSTR5-specific antagonists leads to a loss of protection. The otoprotective effects of pasireotide were also observed in a gentamicin-injured animal model. In vivo studies have shown that 13 days of subcutaneous pasireotide application prevents gentamicin-induced HC death and permanent hearing loss in mice. Auditory brainstem response analysis confirmed the protective effect of pasireotide, and we found a significant threshold shift at all measured frequencies (4, 8, 16, 24, and 32 kHz). Together, these findings indicate that pasireotide is a novel otoprotective peptide acting via the PI3K-Akt pathway and may be of therapeutic value for HC protection from ototoxic insults.
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