ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Cisplatin-induced renal injury is independently mediated by OCT2 and p53.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 73 citations in OpenAlex.
- Possible protective effect of pantoprazole against cisplatin-induced nephrotoxicity in head and neck cancer patients: a randomized controlled trial.Medical oncology (Northwood, London, England) · 2021Trial
- Article
- Research Progress on the Treatment of Renal Injury with Esculetin: Multi-Target Pharmacological Mechanism and Clinical Translation Prospect.International journal of molecular sciences · 2026Review
- An Ex Vivo Patient-Derived Tumor-Bearing Human Kidney Model Recapitulates Drug Toxicity and Metabolic Distribution.Research (Washington, D.C.) · 2026Article
- From Ototoxicity to Otoprotection: Mechanism and Protective Strategies in Cisplatin Therapy.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The Role of Genetic and Non-Genetic Factors in the Occurrence of Cisplatin-Associated Ototoxicity.International journal of molecular sciences · 2025Review
- Platinum-based chemotherapies-induced nephrotoxicity: mechanisms, potential treatments, and management.International urology and nephrology · 2025Review
- Molecular pharmacokinetic mechanism of quercetin-encapsulated polymeric micelles in alleviating cisplatin-induced nephrotoxicity and enhancing antineoplastic effects.Frontiers in pharmacology · 2025Article
- Article
- Mechanistic insights into cisplatin-induced ototoxicity: the central role of transient receptor potential channels.Frontiers in molecular biosciences · 2025Review
- Modulating the Activity of the Human Organic Cation Transporter 2 Emerges as a Potential Strategy to Mitigate Unwanted Toxicities Associated with Cisplatin Chemotherapy.International journal of molecular sciences · 2024Article
- Role of Mouse Organic Cation Transporter 2 for Nephro- and Peripheral Neurotoxicity Induced by Chemotherapeutic Treatment with Cisplatin.International journal of molecular sciences · 2023Article
- Targeting NEDDylation is a Novel Strategy to Attenuate Cisplatin-induced Nephrotoxicity.Cancer research communications · 2023Article
- Can Cisplatin Therapy Be Improved? Pathways That Can Be Targeted.International journal of molecular sciences · 2022Review
- Solute Carrier Transportome in Chemotherapy-Induced Adverse Drug Reactions.Reviews of physiology, biochemistry and pharmacology · 2022Article
- Current Understanding of Membrane Transporters as Regulators or Targets for Cisplatin-Induced Hearing Loss.Molecular pharmacology · 2021Article
- Potential Therapeutic Targets for Cisplatin-Induced Kidney Injury: Lessons from Other Models of AKI and Fibrosis.Journal of the American Society of Nephrology : JASN · 2021Review
- Association of Urine Platinum With Acute Kidney Injury in Children Treated With Cisplatin for Cancer.Journal of clinical pharmacology · 2021Article
- The Mechanism of Drug Nephrotoxicity and the Methods for Preventing Kidney Damage.International journal of molecular sciences · 2021Review
- Suppressed Hepatic Production of Indoxyl Sulfate Attenuates Cisplatin-Induced Acute Kidney Injury in Sulfotransferase 1a1-Deficient Mice.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeTubular secretion of cisplatin is abolished in mice deficient for the organic cation transporters Oct1 and Oct2 (Oct1/2(-/-)mice), and these animals are protected from severe cisplatin-induced kidney damage. Since tubular necrosis is not completely absent in Oct1/2(-/-)mice, we hypothesized that alternate pathways are involved in the observed injury. EXPERIMENTAL
designStudies were done in wild-type, Oct1/2(-/-), or p53-deficient animals, all on an FVB background, receiving cisplatin intraperitoneally at 15 mg/kg. Cisplatin metabolites were analyzed using mass spectrometry, and gene expression was assessed using Affymetrix microarrays and RT-PCR arrays.
resultsKEGG pathway analyses on kidneys from mice exposed to cisplatin revealed that the most significantly altered genes were associated with the p53 signaling network, including Cdnk1a and Mdm2, in both wild-type (P = 2.40 × 10(-11)) and Oct1/2(-/-)mice (P = 1.92 × 10(-8)). This was confirmed by demonstrating that homozygosity for a p53-null allele partially reduced renal tubular damage, whereas loss of p53 in Oct1/2(-/-)mice (p53(-/-)/Oct1/2(-/-)) completely abolished nephrotoxicity. We found that pifithrin-α, an inhibitor of p53-dependent transcriptional activation, inhibits Oct2 and can mimic the lack of nephrotoxicity observed in p53(-/-)/Oct1/2(-/-)mice.
conclusionsThese findings indicate that (i) the p53 pathway plays a crucial role in the kidney in response to cisplatin treatment and (ii) clinical exploration of OCT2 inhibitors may not lead to complete nephroprotection unless the p53 pathway is simultaneously antagonized.
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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.