ArticleAntioxidants (Basel, Switzerland)2020
Nephroprotective Effect of Cilastatin against Gentamicin-Induced Renal Injury In Vitro and In Vivo without Altering Its Bactericidal Efficiency.
Article in Antioxidants (Basel, Switzerland), 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, 35 citations in OpenAlex.
- Megalin: from structure to function.Nature reviews. Nephrology · 2026Review
- Article
- Efficacy of cilastatin sodium in a translational large animal crush syndrome model.Communications medicine · 2026Article
- Cilastatin a promising solution for acute kidney injury by targeting nephrotoxicity.Annals of medicine and surgery (2012) · 2026Article
- Antioxidant Potential and Oxidative Stress Modulation ofPharmaceuticals (Basel, Switzerland) · 2025Article
- Therapeutic Potential of Apocynin: A Promising Antioxidant Strategy for Acute Kidney Injury.Antioxidants (Basel, Switzerland) · 2025Review
- Cilastatin Attenuates Acute Kidney Injury and Reduces Mortality in a Rat Model of Sepsis.International journal of molecular sciences · 2025Article
- Chrysin Attenuates Gentamicin-Induced Renal Injury in Rats Through Modulation of Oxidative Damage and Inflammation via Regulation of Nrf2/AKT and NF-kB/KIM-1 Pathways.Biomedicines · 2025Article
- Nephroprotective Effects of Cilastatin in People at Risk of Acute Kidney Injury: A Systematic Review and Meta-analysis.Kidney medicine · 2024Article
- Nanotherapeutic kidney cell-specific targeting to ameliorate acute kidney injury.Kidney international · 2024Article
- Biomarkers in Contrast-Induced Acute Kidney Injury: Towards A New Perspective.International journal of molecular sciences · 2024Review
- Cilastatin as a Potential Anti-Inflammatory and Neuroprotective Treatment in the Management of Glaucoma.International journal of molecular sciences · 2024Article
- Legal Performance-enhancing Drugs Alter Course and Treatment of Rhabdomyolysis-induced Acute Kidney Injury.Military medicine · 2023Article
- Regulated cell death pathways in kidney disease.Nature reviews. Nephrology · 2023Review
- Shikonin Alleviates Gentamicin-Induced Renal Injury in Rats by Targeting Renal Endocytosis, SIRT1/Nrf2/HO-1, TLR-4/NF-κB/MAPK, and PI3K/Akt Cascades.Antibiotics (Basel, Switzerland) · 2023Article
- Parthenolide Phytosomes Attenuated Gentamicin-Induced Nephrotoxicity in Rats via Activation of Sirt-1, Nrf2, OH-1, and NQO1 Axis.Molecules (Basel, Switzerland) · 2023Article
- Interference with megalin expression/endocytic function by montelukast mitigates gentamicin nephrotoxicity: Downregulation of ClC-5 expression.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Article
- Lipidomics Reveals Cisplatin-Induced Renal Lipid Alterations during Acute Kidney Injury and Their Attenuation by Cilastatin.International journal of molecular sciences · 2021Article
- Ameliorative impacts ofFood science & nutrition · 2021Article
- Effect of Cilastatin on Cisplatin-Induced Nephrotoxicity in Patients Undergoing Hyperthermic Intraperitoneal Chemotherapy.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Gentamicin is a used antibiotic that causes nephrotoxicity in 10-20% of treatment periods, which limits its use considerably. Our results have shown that cilastatin may be a promising therapeutic alternative in toxin-induced acute kidney injury (AKI). Here, we investigated its potential use as a nephroprotector against gentamicin-induced AKI in vitro and in vivo. Porcine renal cells and rats were treated with gentamicin and/or cilastatin. In vivo nephrotoxicity was analyzed by measuring biochemical markers and renal morphology. Different apoptotic, oxidative and inflammatory parameters were studied at cellular and systemic levels. Megalin, mainly responsible for the entry of gentamicin into the cells, was also analyzed. Results show that cilastatin protects cells from gentamicin-induced AKI. Cilastatin decreased creatinine, BUN, kidney injury molecule-1 (KIM-1) and severe morphological changes previously increased by gentamicin in rats. The interference of cilastatin with lipid rafts cycling leads to decreased expression of megalin, and therefore gentamicin uptake and myeloid bodies, resulting in a decrease of apoptotic, oxidative and inflammatory events. Moreover, cilastatin did not prevent bacterial death by gentamicin. Cilastatin reduced gentamicin-induced AKI by preventing key steps in the amplification of the damage, which is associated to the disruption of megalin-gentamicin endocytosis. Therefore, cilastatin might represent a novel therapeutic tool in the prevention and treatment of gentamicin-induced AKI in the clinical setting.
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