ArticleInternational journal of molecular sciences2020
PPAR-α Deletion Attenuates Cisplatin Nephrotoxicity by Modulating Renal Organic Transporters MATE-1 and OCT-2.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Role of solute carrier transporters in the biodistribution and toxicity of chemotherapeutic drugs.Pharmacological reviews · 2026Review
- Icaritin Ameliorates Cisplatin-Induced Mitochondrial Metabolic Dysfunction-Associated Nephrotoxicity and Synergistically Potentiates Its Antitumor Efficacy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mitochondrial dysfunction and metabolic reprogramming in acute kidney injury: mechanisms, therapeutic advances, and clinical challenges.Frontiers in physiology · 2025Review
- The Protective Effect of Omeprazole on Vancomycin Cytotoxicity in HK-2 Cells and Renal Injury in Rats.BioMed research international · 2025Article
- Molecular pharmacokinetic mechanism of quercetin-encapsulated polymeric micelles in alleviating cisplatin-induced nephrotoxicity and enhancing antineoplastic effects.Frontiers in pharmacology · 2025Article
- Molecular mechanisms of cisplatin resistance in ovarian cancer.Genes & diseases · 2024Review
- Focus on Mitochondrial Respiratory Chain: Potential Therapeutic Target for Chronic Renal Failure.International journal of molecular sciences · 2024Review
- The underlying mechanisms of cisplatin-induced nephrotoxicity and its therapeutic intervention using natural compounds.Naunyn-Schmiedeberg's archives of pharmacology · 2023Review
- Polymorphic renal transporters and cisplatin's toxicity in urinary bladder cancer patients: current perspectives and future directions.Medical oncology (Northwood, London, England) · 2023Review
- NOX4 is a potential therapeutic target in septic acute kidney injury by inhibiting mitochondrial dysfunction and inflammation.Theranostics · 2023Article
- Istradefylline protects from cisplatin-induced nephrotoxicity and peripheral neuropathy while preserving cisplatin antitumor effects.The Journal of clinical investigation · 2022Article
- Article
- The System Profile of Renal Drug Transporters in Tubulointerstitial Fibrosis Model and Consequent Effect on Pharmacokinetics.Molecules (Basel, Switzerland) · 2022Article
- Troxerutin alleviates kidney injury in rats via PI3K/AKT pathway by enhancing MAP4 expression.Food & nutrition research · 2022Article
- Article
- Cisplatin Mouse Models: Treatment, Toxicity and Translatability.Biomedicines · 2021Review
- The role of metabolic reprogramming in tubular epithelial cells during the progression of acute kidney injury.Cellular and molecular life sciences : CMLS · 2021Review
- Physiology, Biochemistry, and Pharmacology of Transporters for Organic Cations.International journal of molecular sciences · 2021Article
- Glucose Metabolism in Acute Kidney Injury and Kidney Repair.Frontiers in medicine · 2021Review
- Drug Transporters in the Kidney: Perspectives on Species Differences, Disease Status, and Molecular Docking.Frontiers in pharmacology · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Cisplatin is a chemotherapy drug widely used in the treatment of solid tumors. However, nephrotoxicity has been reported in about one-third of patients undergoing cisplatin therapy. Proximal tubules are the main target of cisplatin toxicity and cellular uptake; elimination of this drug can modulate renal damage. Organic transporters play an important role in the transport of cisplatin into the kidney and organic cations transporter 2 (OCT-2) has been shown to be one of the most important transporters to play this role. On the other hand, multidrug and toxin extrusion 1 (MATE-1) transporter is the main protein that mediates the extrusion of cisplatin into the urine. Cisplatin nephrotoxicity has been shown to be enhanced by increased OCT-2 and/or reduced MATE-1 activity. Peroxisome proliferator-activated receptor alpha (PPAR-α) is the transcription factor which controls lipid metabolism and glucose homeostasis; it is highly expressed in the kidneys and interacts with both MATE-1 and OCT-2. Considering the above, we treated wild-type and PPAR-α knockout mice with cisplatin in order to evaluate the severity of nephrotoxicity. Cisplatin induced renal dysfunction, renal inflammation, apoptosis and tubular injury in wild-type mice, whereas PPAR-α deletion protected against these alterations. Moreover, we observed that cisplatin induced down-regulation of organic transporters MATE-1 and OCT-2 and that PPAR-α deletion restored the expression of these transporters. In addition, PPAR-α knockout mice at basal state showed increased MATE-1 expression and reduced OCT-2 levels. Here, we show for the first time that PPAR-α deletion protects against cisplatin nephrotoxicity and that this protection is via modulation of the organic transporters MATE-1 and OCT-2.
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