ArticleJournal of the American Society of Nephrology : JASN2020
Gentamicin-Induced Acute Kidney Injury in an Animal Model Involves Programmed Necrosis of the Collecting Duct.
Article in Journal of the American Society of Nephrology : JASN, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 76 citations in OpenAlex.
- Ellagic Acid Attenuates Gentamicin Nephrotoxicity by Integrated Modulation of ER Stress-Associated Apoptosis-Autophagy Crosstalk and Attenuation of Nrf2/HO-1 Signaling.Biomedicines · 2026Article
- Caloric Restriction Attenuates Gentamicin-Induced Acute Kidney Injury and Is Associated with Changes in Oxidative Stress and Mitochondrial DNA Damage.Antioxidants (Basel, Switzerland) · 2026Article
- ELMO1 dependent efferocytosis protects from nephrotoxin induced acute kidney injury.Cell death discovery · 2026Article
- Paraxanthine and azilsartan attenuate gentamicin-induced renal fibrosis via modulation of TGF-β1/Smad3/7 signaling and miRNA-21/miRNA-200b expression.Journal of translational medicine · 2026Article
- In vitro modeling of renal injury-induced cardiac effects using human iPSC-derived organoids.Cell communication and signaling : CCS · 2026Article
- Targeting the powerhouse: the mitochondrial perspective on gentamicin-induced kidney injury.Archives of toxicology · 2026Review
- Local Surgicel/rhBMP-7 delivery is associated with renal repair responses after surgically induced acute kidney injury.Frontiers in medicine · 2026Article
- Evaluation of the protective role ofOpen veterinary journal · 2025Article
- Induction of Nephron-Ductal Dual Lineages via Early Retinoic Acid Signaling Establishes a Platform for Fully Patterned Kidney Organoids.Advanced healthcare materials · 2025Article
- Preventive and Protective Role of Pomegranate Fruit Extract (Punica granatum) on Gentamicin-induced Side Effects in Wistar rats.Cell biochemistry and biophysics · 2025Article
- Reversible compromise of physiological resilience by accumulation of heteroplasmic mtDNA mutations.Science (New York, N.Y.) · 2025Article
- Multiparametric Evaluation of Drug-Induced Acute Kidney Injury Using Preclinical 7T Magnetic Resonance Imaging in Rat Models.Metabolites · 2025Article
- Effects of Peptides and Bioactive Peptides on Acute Kidney Injury: A Review Study.Iranian biomedical journal · 2025Review
- Clopidogrel protects against gentamicin-induced nephrotoxicity through targeting oxidative stress, apoptosis, and coagulation pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Evaluation of Single and Multi-Strain Probiotics with Gentamicin AgainstMicroorganisms · 2025Article
- Enriched human embryonic stem cells-derived CD133Regenerative therapy · 2024Article
- Recent Advancements in MXene-Based Biosensors for Health and Environmental Applications-A Review.Biosensors · 2024Review
- Monoterpene linalool restrains gentamicin-mediated acute kidney injury in rats by subsiding oxidative stress, apoptosis, and the NF-κB/iNOS/TNF-α/IL-1β pathway and regulating TGF-β.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Amoxicillin and Ceftriaxone: A Synergistic Association AgainstOpen forum infectious diseases · 2024Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundGentamicin is a potent aminoglycoside antibiotic that targets gram-negative bacteria, but nephrotoxicity limits its clinical application. The cause of gentamicin-induced AKI has been attributed mainly to apoptosis of the proximal tubule cells. However, blocking apoptosis only partially attenuates gentamicin-induced AKI in animals.
methodsMice treated with gentamicin for 7 days developed AKI, and programmed cell death pathways were examined using pharmacologic inhibitors and in RIPK3-deficient mice. Effects in porcine and murine kidney cell lines were also examined.
resultsGentamicin caused a low level of apoptosis in the proximal tubules and significant ultrastructural alterations consistent with necroptosis, occurring predominantly in the collecting ducts (CDs), including cell and organelle swelling and rupture of the cell membrane. Upregulation of the key necroptotic signaling molecules, mixed lineage kinase domain-like pseudokinase (MLKL) and receptor-interacting serine/threonine-protein kinase 3 (RIPK3), was detected in gentamicin-treated mice and in cultured renal tubule cells. In addition, gentamicin induced apical accumulation of total and phosphorylated MLKL (pMLKL) in CDs in mouse kidney. Inhibiting a necroptotic protein, RIPK1, with necrostatin-1 (Nec-1), attenuated gentamicin-induced necrosis and upregulation of MLKL and RIPK3 in mice and cultured cells. Nec-1 also alleviated kidney inflammation and fibrosis, and significantly improved gentamicin-induced renal dysfunction in mice. Furthermore, deletion of RIPK3 in the
conclusionsA previously unrecognized role of programmed necrosis in collecting ducts in gentamicin-induced kidney injury presents a potential new therapeutic strategy to alleviate gentamicin-induced AKI through inhibiting necroptosis.
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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.