ArticleOncotarget2018
Oxaliplatin-induced blood brain barrier loosening: a new point of view on chemotherapy-induced neurotoxicity.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- Neurocognitive Effects of Chemotherapy for Colorectal Cancer: A Systematic Review and a Meta-Analysis of 11 Studies.Cancer research and treatment · 2021Pooled it
- Methylnaltrexone Treatment for Opioid-Induced Constipation in Patients with and without Cancer: Effect of Initial Dose.Journal of pain research · 2023Trial
- 3D Bioprinted Blood-Brain-Tumor Barrier Spheroid-Based In Situ Evaluation of Anticancer Compounds Against Glioblastoma: ROS-Producing Ruthenium as a Potential Therapeutic Candidate.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cancer therapy-related cognitive impairment, part 1: an integrative clinical-mechanistic framework from phenotypes to convergent neurobiological pathways.Pharmacological reports : PR · 2026Review
- Chemotherapy neurotoxicity and aging: Uncovering shared central nervous system pathologies and potential interventions.Neuro-oncology advances · 2026Review
- Influence of ApoE genotype on doxorubicin-induced cognitive impairment in juvenile rats.Scientific reports · 2025Article
- Omega-3 fatty acids and chemotherapy-induced toxicities: mechanisms and emerging evidence with a pediatric focus.Nutrition & metabolism · 2025Review
- The effects of doxorubicin on blood-brain barrier integrity in hCMEC/D3.Neurotoxicology · 2025Article
- Persisting blood-brain barrier disruption following cisplatin treatment in a mouse model of chemotherapy-associated cognitive impairment.GeroScience · 2025Article
- Pt(IV) Complexes as Anticancer Drugs and Their Relationship with Oxidative Stress.Biomedicines · 2025Review
- Platinum Deposition in the Central Nervous System: A Novel Insight into Oxaliplatin-induced Peripheral Neuropathy in Young and Old Mice.Molecular neurobiology · 2025Article
- Nose-to-brain Drug Delivery System: An Emerging Approach to Chemotherapy-induced Cognitive Impairment.Pharmaceutical nanotechnology · 2025Review
- Effects of preoperative neoadjuvant chemotherapy on postoperative delirium in patients with gynecological tumor surgery: an observational study.Journal of cancer research and clinical oncology · 2024Observational
- Biological Mediators and Partial Regulatory Mechanisms on Neuropathic Pain Associated With Chemotherapeutic Agents.Physiological research · 2024Review
- Discovery and Preclinical Evaluation of a Novel Inhibitor of FABP5, ART26.12, Effective in Oxaliplatin-Induced Peripheral Neuropathy.The journal of pain · 2024Article
- The chemotherapeutic agent doxorubicin induces brain senescence, with modulation by APOE genotype.Experimental neurology · 2024Article
- Huangqi Guizhi Wuwu Decoction Improves Inflammatory Factor Levels in Chemotherapy-induced Peripheral Neuropathy by Regulating the Arachidonic Acid Metabolic Pathway.Current pharmaceutical design · 2024Article
- β-Caryophyllene Inhibits Oxaliplatin-Induced Peripheral Neuropathy in Mice: Role of Cannabinoid Type 2 Receptors, Oxidative Stress and Neuroinflammation.Antioxidants (Basel, Switzerland) · 2023Article
- Prevention of Chemotherapy-Induced Peripheral Neuropathy by Inhibiting C-X-C Motif Chemokine Receptor 2.International journal of molecular sciences · 2023Article
- Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxaliplatin is a key drug in the treatment of advanced metastatic colorectal cancer. Despite its beneficial effects in tumor reduction, the most prevalent side-effect of oxaliplatin treatment is a chemotherapy-induced neuropathy that frequently forces to discontinue the therapy. Indeed, along with direct damage to peripheral nerves, the chemotherapy-related neurotoxicity involves also the central nervous system (CNS) as demonstrated by pain chronicity and cognitive impairment (also known as chemobrain), a newly described pharmacological side effect. The presence of the blood brain barrier (BBB) is instrumental in preventing the entry of the drug into the CNS; here we tested the hypothesis that oxaliplatin might enter the endothelial cells of the BBB vessels and trigger a signaling pathway that induce the disassembly of the tight junctions, the critical components of the BBB integrity. By using a rat brain endothelial cell line (RBE4) we investigated the signaling pathway that ensued the entry of oxaliplatin within the cell. We found that the administration of 10 μM oxaliplatin for 8 and 16 h induced alterations of the tight junction (TJs) proteins zonula occludens-1 (ZO-1) and of F-actin, thus highlighting BBB alteration. Furthermore, we reported that intracellular oxaliplatin rapidly induced increased levels of reactive oxygen species and endoplasmic reticulum stress, assessed by the evaluation of glucose-regulated protein GRP78 expression levels. These events were accompanied by activation of caspase-3 that led to extracellular ATP release. These findings suggested a possible novel mechanism of action for oxaliplatin toxicity that could explain, at least in part, the chemotherapy-related central effects.
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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.