ArticleEMBO reports2021
Toll-like receptor 4 is activated by platinum and contributes to cisplatin-induced ototoxicity.
Article in EMBO reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
34 citing papers in PubMed, 49 citations in OpenAlex.
- Apigenin Protects Against Cisplatin-Induced Cardiotoxicity: Potential Involvement of CD38-Sirt3 Signaling in Rats.Molecules (Basel, Switzerland) · 2026Article
- Navigating the Genetic Risk of Chemotherapy-Induced Hearing Loss in the Stria Vascularis.Clinical pharmacology and therapeutics · 2026Review
- Toward Smart Salivary Diagnostics: A Comprehensive Review of Heavy Metal Biomarkers and Digital Risk Modeling.Diagnostics (Basel, Switzerland) · 2026Review
- Genetic and Environmental Factors Shaping Hearing Loss: Xenobiotics, Mechanisms and Translational Perspectives.Journal of xenobiotics · 2026Review
- Protective effect of hesperetin against myelosuppression and splenic inflammation via modulating TLR4/MYD88/NF-κB signaling: molecular docking and experimental validation.Frontiers in pharmacology · 2026Article
- Coconut oil/lauric acid-based nanodrug formulation: a multifunctional platform for enhancing cancer therapy and mitigating toxicity.Frontiers in cell and developmental biology · 2026Review
- Pharmacological Inhibition of JAK/STAT-IL2 Axis Alleviated Cisplatin-Induced Ototoxicity.Molecular neurobiology · 2025Article
- Krill Oil Mitigates Cisplatin-Induced Ovarian Toxicity via Attenuation of Oxidative Stress and Inflammatory Pathways.Current issues in molecular biology · 2025Article
- Metal coordination polymer nanoparticles for cancer therapy.Essays in biochemistry · 2025Review
- Mechanistic insights into chemotherapy-induced circadian disruption using rodent models.Trends in neurosciences · 2025Review
- GSDMD-mediated mitochondrial dysfunction in marginal cells: A potential driver of inflammation and stria vascularis damage in CIHL.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Inhibition of the cGAS‑STING Pathway Reduces Cisplatin-Induced Inner Ear Hair Cell Damage.Neuroscience bulletin · 2025Article
- S100A8 as a potential therapeutic target for cancer metastasis.Cancer science · 2025Review
- Studies on the mechanism of ototoxic action of cisplatin and the antagonistic effect of polyphenolic compounds.Frontiers in pharmacology · 2025Review
- Adopting orphan receptors: zebrafish Tlr4 homologs mediate responses to group IX/X transition metals.Frontiers in immunology · 2025Article
- Enhancing biocompatibility of the brain-machine interface: A review.Bioactive materials · 2024Review
- CORM‑2 reduces cisplatin accumulation in the mouse inner ear and protects against cisplatin-induced ototoxicity.Journal of advanced research · 2024Article
- Strategies for the development of metalloimmunotherapies.Nature biomedical engineering · 2024Review
- Intracellular Survival and Pathogenicity Modulation ofInternational journal of molecular sciences · 2024Article
- Protein Haptenation and Its Role in Allergy.Chemical research in toxicology · 2024Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Toll-like receptor 4 (TLR4) recognizes bacterial lipopolysaccharide (LPS) and can also be activated by some Group 9/10 transition metals, which is believed to mediate immune hypersensitivity reactions. In this work, we test whether TLR4 can be activated by the Group 10 metal platinum and the platinum-based chemotherapeutic cisplatin. Cisplatin is invaluable in childhood cancer treatment but its use is limited due to a permanent hearing loss (cisplatin-induced ototoxicity, CIO) adverse effect. We demonstrate that platinum and cisplatin activate pathways downstream of TLR4 to a similar extent as the known TLR4 agonists LPS and nickel. We further show that TLR4 is required for cisplatin-induced inflammatory, oxidative, and cell death responses in hair cells in vitro and for hair cell damage in vivo. Finally, we identify a TLR4 small molecule inhibitor able to curtail cisplatin toxicity in vitro. Thus, our findings indicate that TLR4 is a promising therapeutic target to mitigate CIO.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.