ArticleScientific reports2024
Nobiletin alleviates cisplatin-induced ototoxicity via activating autophagy and inhibiting NRF2/GPX4-mediated ferroptosis.
Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Cisplatin-induced oxidative stress and ferroptosis-associated injury in retinal pigment epithelial cells attenuated by Toxoplasma gondii infection.Genes & genomics · 2026Article
- Circadian-Related Serotonin/Melatonin Level Modulates Cisplatin Ototoxicity Susceptibility Depended on NOS3-NO Pathway.Journal of pineal research · 2026Article
- Nobiletin enhances Doxorubicin sensitivity in osteosarcoma through ER stress-induced apoptosis mediated by the PI3K/AKT pathway.Scientific reports · 2026Article
- Autophagy in Sensorineural Hearing Loss: Jekyll or Hyde?International journal of molecular sciences · 2026Review
- Autophagy-Ferroptosis Interplay Network: Redefining Therapeutic Paradigms for Diabetic Wound Healing.Journal of inflammation research · 2026Review
- Baicalin attenuates cisplatin-induced cochlear hair cell damage by modulating the ROS-p38 MAPK signaling pathway.Frontiers in cell and developmental biology · 2026Article
- 4-Methoxylonchocarpin protects against cisplatin induced acute kidney injury via regulating ferroptosis.Renal failure · 2025Article
- Ferroptosis and hearing loss: from molecular mechanisms to therapeutic interventions.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Polyphenolic compounds as protective agents against cisplatin-induced ototoxicity with molecular mechanisms and clinical potential.RSC medicinal chemistry · 2025Review
- Co-administration of nobiletin and tetrahydrocurcumin enhanced the cytotoxicity to breast cancer through inhibiting CYP1A1 enzyme: from the perspective of pharmacokinetic interactions.Discover oncology · 2025Article
- DLK/JNK3 Upregulation Aggravates Hair Cell Senescence in Mice Cochleae via Excessive Autophagy.Aging cell · 2025Article
- The Role and Mechanism of GSDME-Dependent Pyroptosis in Cochlear Marginal Cells Injury by Cisplatin.Biomedicines · 2025Article
- Possible Mitigating Effect of Nobiletin on Rotenone-Induced Parkinsonism in Male Albino Rat Model: Targeting Bmal1/Nrf2 Mediated Ferroptosis and Restoring Mitochondrial Mitophagy.Neurochemical research · 2025Article
- Mechanisms of ferroptotic and non-ferroptotic organ toxicity of chemotherapy: protective and therapeutic effects of ginger, 6-gingerol and zingerone in preclinical studies.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Article
- Metabolomic and Cellular Mechanisms of Drug-Induced Ototoxicity and Nephrotoxicity: Therapeutic Implications of Uric Acid Modulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Studies on the mechanism of ototoxic action of cisplatin and the antagonistic effect of polyphenolic compounds.Frontiers in pharmacology · 2025Review
- Natural products targeting ferroptosis in cancer: molecular mechanisms and applications.Frontiers in oncology · 2025Review
- Resveratrol Reduces Cisplatin-induced Cochlear Hair Cell Pyroptosis by Inhibiting the mtROS/TXNIP/NLRP3 Pathway.Combinatorial chemistry & high throughput screening · 2025Article
- Cisplatin-Induced Hearing Loss, Oxidative Stress, and Antioxidants as a Therapeutic Strategy-A State-of-the-Art Review.Antioxidants (Basel, Switzerland) · 2024Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Nobiletin, a citrus polymethoxy flavonoid with antiapoptotic and antioxidative properties, could safeguard against cisplatin-induced nephrotoxicity and neurotoxicity. Cisplatin, as the pioneer of anti-cancer drug, the severe ototoxicity limits its clinical applications, while the effect of nobiletin on cisplatin-induced ototoxicity has not been identified. The current study investigated the alleviating effect of nobiletin on cisplatin-induced ototoxicity and the underlying mechanisms. Apoptosis and ROS formation were evaluated using the CCK-8 assay, Western blotting, and immunofluorescence, indicating that nobiletin attenuated cisplatin-induced apoptosis and oxidative stress. LC3B and SQSTM1/p62 were determined by Western blotting, qPCR, and immunofluorescence, indicating that nobiletin significantly activated autophagy. Nobiletin promoted the nuclear translocation of NRF2 and the transcription of its target genes, including Hmox1, Nqo1, and ferroptosis markers (Gpx4, Slc7a11, Fth, and Ftl), thereby inhibiting ferroptosis. Furthermore, RNA sequencing analysis verified that autophagy, ferroptosis, and the NRF2 signaling pathway served as crucial points for the protection of nobiletin against ototoxicity caused by cisplatin. Collectively, these results indicated, for the first time, that nobiletin alleviated cisplatin-elicited ototoxicity through suppressing apoptosis and oxidative stress, which were attributed to the activation of autophagy and the inhibition of NRF2/GPX4-mediated ferroptosis. Our study suggested that nobiletin could be a prospective agent for preventing cisplatin-induced hearing loss.
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Registered trials
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