ArticleThe American journal of pathology2014
Transgenic expression of the human MRP2 transporter reduces cisplatin accumulation and nephrotoxicity in Mrp2-null mice.
Article in The American journal of pathology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 60 citations in OpenAlex.
- Population Pharmacokinetic Model of Platinum Disposition in Cancer Patients Receiving Cisplatin and Randomized to 5-HTJournal of clinical pharmacology · 2025Trial
- Advances regarding physiological functions and mechanisms of theaflavin‑3,3'‑digallate (Review).Molecular medicine reports · 2026Review
- Review
- Mechanistic insights into cisplatin-induced ototoxicity: the central role of transient receptor potential channels.Frontiers in molecular biosciences · 2025Review
- Understanding Cisplatin Pharmacokinetics and Toxicodynamics to Predict and Prevent Kidney Injury.The Journal of pharmacology and experimental therapeutics · 2024Review
- Nonalcoholic steatohepatitis increases plasma retention of sorafenib-glucuronide in a mouse model by altering hepatocyte hopping.Acta pharmaceutica Sinica. B · 2024Article
- The underlying mechanisms of cisplatin-induced nephrotoxicity and its therapeutic intervention using natural compounds.Naunyn-Schmiedeberg's archives of pharmacology · 2023Review
- Structural Optimization of Platinum Drugs to Improve the Drug-Loading and Antitumor Efficacy of PLGA Nanoparticles.Pharmaceutics · 2022Article
- Small-molecule inhibitors, immune checkpoint inhibitors, and more: FDA-approved novel therapeutic drugs for solid tumors from 1991 to 2021.Journal of hematology & oncology · 2022Review
- Epigenomic and transcriptomic analyses define core cell types, genes and targetable mechanisms for kidney disease.Nature genetics · 2022Article
- Regulation of renal calbindin expression during cisplatin-induced kidney injury.Journal of biochemical and molecular toxicology · 2022Article
- Current Understanding of Membrane Transporters as Regulators or Targets for Cisplatin-Induced Hearing Loss.Molecular pharmacology · 2021Article
- Association of Urine Platinum With Acute Kidney Injury in Children Treated With Cisplatin for Cancer.Journal of clinical pharmacology · 2021Article
- Review
- A Canadian Study of Cisplatin Metabolomics and Nephrotoxicity (ACCENT): A Clinical Research Protocol.Canadian journal of kidney health and disease · 2021Article
- The rediscovery of platinum-based cancer therapy.Nature reviews. Cancer · 2021Review
- The Mechanisms of Yu Ping Feng San in Tracking the Cisplatin-Resistance by Regulating ATP-Binding Cassette Transporter and Glutathione S-Transferase in Lung Cancer Cells.Frontiers in pharmacology · 2021Article
- Elevated N-Glycosylation Contributes to the Cisplatin Resistance of Non-Small Cell Lung Cancer Cells Revealed by Membrane Proteomic and Glycoproteomic Analysis.Frontiers in pharmacology · 2021Article
- Identification of Novel Biomarkers for Predicting Kidney Injury Due to Drugs Using "Omic" Strategies.Pharmacogenomics and personalized medicine · 2020Review
- Recent Advances in Models, Mechanisms, Biomarkers, and Interventions in Cisplatin-Induced Acute Kidney Injury.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The chemotherapeutic drug cisplatin is actively transported into proximal tubules, leading to acute renal injury. Previous studies suggest that the multidrug resistance-associated protein 2 (Mrp2) transporter may efflux cisplatin conjugates from cells. We sought to determine whether the absence of Mrp2 alters the accumulation and toxicity of platinum in the kidneys of mice and whether transgenic expression of the human MRP2 gene could protect against cisplatin injury in vivo. Plasma, kidneys, and livers from vehicle- and cisplatin-treated wild-type and Mrp2-null mice were collected for quantification of platinum and toxicity. By 24 hours, twofold higher concentrations of platinum were detected in the kidneys and livers of Mrp2-null mice compared with wild types. Enhanced platinum concentrations in Mrp2-null mice were observed in DNA and cytosolic fractions of the kidneys. Four days after cisplatin treatment, more extensive proximal tubule injury was observed in Mrp2-null mice compared with wild-type mice. Kidneys from naive Mrp2-null mice had elevated glutathione S-transferase mRNA levels, which could increase the formation of cisplatin-glutathione conjugates that may be metabolized to toxic thiol intermediates. Transgenic expression of the human MRP2 gene in Mrp2-null mice reduced the accumulation and nephrotoxicity of cisplatin to levels observed in wild-type mice. These data suggest that deficiency in Mrp2 lowers platinum excretion and increases susceptibility to kidney injury, which can be rescued by the human MRP2 ortholog.
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