ArticleOxidative medicine and cellular longevity2022
Regulation of ACSL4-Catalyzed Lipid Peroxidation Process Resists Cisplatin Ototoxicity.
Article in Oxidative medicine and cellular longevity, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Myocardial Ischemia-Reperfusion Injury: Molecular Mechanisms and Innovative Therapeutic Strategies.Reviews in cardiovascular medicine · 2026Review
- Paeonol Alleviate Cisplatin- and Noise-Induced Hearing Loss by Preserving Hair Cell Ribosome Biogenesis.CNS neuroscience & therapeutics · 2026Article
- Rutin-Functionalized Selenium Nanoparticles Attenuate Cisplatin-Induced Cardiohepatic Injury in Rats: Modulation of ER Stress-Related Gene Expression and Mitochondrial Apoptotic Markers.International journal of molecular sciences · 2026Article
- Ovarian Cancer Stem Cells: Mechanisms of Progression and Therapeutic Strategies.Oncology research · 2026Review
- Targeting Phospholipid Metabolism as an Effective Hearing Protection Strategy.Neuroscience bulletin · 2026Article
- MCPB-21 targets glycogenin-2 to regulate fatty acid oxidation and promote ferroptosis of breast cancer.American journal of cancer research · 2026Article
- Ferroptosis in veterinary medicine: mechanisms, therapies, and unmet challenges.The veterinary quarterly · 2025Review
- Ferroptosis and hearing loss: from molecular mechanisms to therapeutic interventions.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- From Ototoxicity to Otoprotection: Mechanism and Protective Strategies in Cisplatin Therapy.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Pinoresinol Diglucoside Attenuates Nuclear Receptor Coactivator 4-Mediated Ferritinophagy Associated with Cisplatin-Induced Hearing Loss.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Differential ferroptosis regulation in red and white gastrocnemius under obesity and its Attenuation by exercise and dietary restriction.Scientific reports · 2025Article
- The role of ACSL4 in stroke: mechanisms and potential therapeutic target.Molecular and cellular biochemistry · 2025Review
- Resveratrol alleviates testicular toxicity induced by anti-PD-1 through regulating the NRF2-SLC7A11-GPX4 pathway.Frontiers in immunology · 2025Article
- Ferroptosis, oxidative stress and hearing loss: Mechanistic insights and therapeutic opportunities.Heliyon · 2024Review
- TCP1 expression alters the ferroptosis sensitivity of diffuse large B-cell lymphoma subtypes by stabilising ACSL4 and influences patient prognosis.Cell death & disease · 2024Article
- FDA-Approved Tedizolid Phosphate Prevents Cisplatin-Induced Hearing Loss Without Decreasing Its Anti-tumor Effect.Journal of the Association for Research in Otolaryngology : JARO · 2024Article
- The application of approaches in detecting ferroptosis.Heliyon · 2024Review
- Advances in Ferroptosis-Inducing Agents by Targeted Delivery System in Cancer Therapy.International journal of nanomedicine · 2024Review
- Aqueous humor metabolomic profiling identifies a distinct signature in pseudoexfoliation syndrome.Frontiers in molecular biosciences · 2024Article
- Therapeutic effects of natural compounds against diabetic complications via targeted modulation of ferroptosis.Frontiers in pharmacology · 2024Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cisplatin-induced ototoxicity is one of the common side effects during its treatment and there are no effective measures to prevent it. Our study aimed to investigate the effect of ACSL4-catalyzed lipid peroxidation on cisplatin-induced hearing loss and its possible protective mechanisms. We used a variety of cisplatin ototoxicity models, including HEI-OC1 cell line, cochlear explants, and ET4 GFP+ zebrafish. After measuring the experimental concentrations of cisplatin by CCK8 assay and immunofluorescence, respectively, we examined the levels of lipid peroxidation by MDA content, 4-HNE content, and C11-BODIPY (581/591) probe. Then, we used two ferroptosis inhibitors, FER-1, and Vit-E to protect hair cells. We found that cisplatin significantly increased the levels of lipid peroxidation and that this process can be resisted by the ferroptosis inhibitors. Afterwards, we performed metabolomic assays on the cisplatin-treated hair cells. The metabolite levels were significantly altered in the experimental group compared to the control group, and the highest degree of change was observed in the glutathione metabolic pathway and the arachidonic acid metabolic pathway. Therefore, we screened the key enzymes on the arachidonic acid metabolic pathway in the hair cells after cisplatin treatment and found that ACSL4 had the greatest regulatory value. Further, we reduced the level of lipid peroxide in hair cells by specifically inhibiting the expression of ACSL4, which protected hair cells from cisplatin damage at source. In conclusion, the lipid peroxidation process regulated by ACSL4 may be an important factor contributing to the sensitivity of hair cells to cisplatin. Inhibition of ACSL4 expression may be an effective preventive measure against cisplatin ototoxicity.
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