ArticleBritish journal of pharmacology2020
Protective effect of cilastatin against diclofenac-induced nephrotoxicity through interaction with diclofenac acyl glucuronide via organic anion transporters.
Article in British journal of pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- Activation of sirtuin 3 and maintenance of mitochondrial homeostasis by artemisinin protect against diclofenac-induced kidney injury in rats.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Renal organic anion transporter 1: clinical relevance and the underlying mechanisms in chronic kidney disease.BMC nephrology · 2025Review
- Impact of Species and Tissue Differences on In Vitro Glucuronidation of Diclofenac.Molecules (Basel, Switzerland) · 2024Article
- VARIDT 3.0: the phenotypic and regulatory variability of drug transporter.Nucleic acids research · 2024Article
- Anti-inflammatory activity of novel derivatives of pyrazolo [3,4d] pyridazine against digestive system inflammation.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Recent Advances in Synthetic Drugs and Natural Actives Interacting with OAT3.Molecules (Basel, Switzerland) · 2023Review
- DrugMAP: molecular atlas and pharma-information of all drugs.Nucleic acids research · 2023Article
- The Flavonoid Hesperidin Methyl Chalcone Targets Cytokines and Oxidative Stress to Reduce Diclofenac-Induced Acute Renal Injury: Contribution of the Nrf2 Redox-Sensitive Pathway.Antioxidants (Basel, Switzerland) · 2022Article
- A Single Oral Dose of Diclofenac Causes Transition of Experimental Subclinical Acute Kidney Injury to Chronic Kidney Disease.Biomedicines · 2022Article
- Oral Proteasomal Inhibitors Ixazomib, Oprozomib, and Delanzomib Upregulate the Function of Organic Anion Transporter 3 (OAT3): Implications in OAT3-Mediated Drug-Drug Interactions.Pharmaceutics · 2021Article
- The Role of Uptake and Efflux Transporters in the Disposition of Glucuronide and Sulfate Conjugates.Frontiers in pharmacology · 2021Review
- Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate Sepsis-Induced Acute Kidney Injury by Promoting Mitophagy of Renal Tubular Epithelial CellsFrontiers in endocrinology · 2021Article
- Protective effect of cilastatin against diclofenac-induced nephrotoxicity through interaction with diclofenac acyl glucuronide via organic anion transporters.British journal of pharmacology · 2020Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
background and purposeDiclofenac is a widely used nonsteroidal anti-inflammatory drug. However, adverse effects in the kidney limit its clinical application. The present study was aimed to evaluate the potential effect of cilastatin on diclofenac-induced acute kidney injury and to clarify the potential roles of renal organic anion transporters (OATs) in the drug-drug interaction between cilastatin and diclofenac. EXPERIMENTAL APPROACH: The effect of cilastatin was evaluated in diclofenac-induced acute kidney injury in mice. Human OAT1/3-transfected HEK293 cells and renal primary proximal tubule cells (RPTCs) were used to investigate OAT1/3-mediated transport and the cytotoxicity of diclofenac. KEY
resultsCilastatin treatment decreased the pathological changes, renal dysfunction and elevated renal levels of oxidation products, cytokine production and apoptosis induced by diclofenac in mice. Moreover, cilastatin increased the plasma concentration and decreased the renal distribution of diclofenac and its glucuronide metabolite, diclofenac acyl glucuronide (DLF-AG). Similarly, cilastatin inhibited cytotoxicity and mitochondrial damage in RPTCs but did not change the intracellular accumulation of diclofenac. DLF-AG but not diclofenac exhibited OAT-dependent cytotoxicity and was identified as an OAT1/3 substrate. Cilastatin inhibited the intracellular accumulation and decreased the cytotoxicity of DLF-AG in RPTCs. CONCLUSION AND IMPLICATIONS: Cilastatin alleviated diclofenac-induced acute kidney injury in mice by restoring the redox balance, suppressing inflammation, and reducing apoptosis. Cilastatin inhibited OATs and decreased the renal distribution of diclofenac and DLF-AG, which further ameliorated the diclofenac-induced nephrotoxicity in mice. Cilastatin can be potentially used in the clinic as a therapeutic agent to alleviate the adverse renal reaction to diclofenac.
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