ArticleAntimicrobial agents and chemotherapy2009
Amphotericin B-induced renal tubular cell injury is mediated by Na+ Influx through ion-permeable pores and subsequent activation of mitogen-activated protein kinases and elevation of intracellular Ca2+ concentration.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 44 citations in OpenAlex.
- Coxsackievirus A6 infection exacerbates kidney injury in mice through the p38-MAPK pathway.Virology journal · 2026Article
- Kidneys on the Frontline: Nephrologists Tackling the Wilds of Acute Kidney Injury in Trauma Patients-From Pathophysiology to Early Biomarkers.Diagnostics (Basel, Switzerland) · 2025Review
- Kidney Toxicity of Drugs for the Heart: An Updated Perspective.Metabolites · 2025Review
- Regulation of renal nitric oxide and eNOS/iNOS expression by tadalafil participates in the mitigation of amphotericin B-induced renal injury: Down-regulation of NF-κB/iNOS/caspase-3 signaling.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Conventional amphotericin B elicits markers of immunogenic cell death on leukemic blasts, mediates immunostimulatory effects on phagocytic cells, and synergizes with PD-L1 blockade.Oncoimmunology · 2022Article
- Could dantrolene be explored as a repurposed drug to treat COVID-19 patients by restoring intracellular calcium homeostasis?European review for medical and pharmacological sciences · 2020Article
- Lipid Systems for the Delivery of Amphotericin B in Antifungal Therapy.Pharmaceutics · 2020Review
- Amphotericin B potentiates the anticancer activity of doxorubicin on the MCF-7 breast cancer cells.Journal of chemical biology · 2017Article
- Protective and antifungal properties of Nanodisk-Amphotericin B over commercially available Amphotericin B.World journal of otorhinolaryngology - head and neck surgery · 2017Article
- Brief Report: Effects of Tenofovir and Amphotericin B Deoxycholate Coadministration on Kidney Function in Patients Treated for Cryptococcal Meningitis.Journal of acquired immune deficiency syndromes (1999) · 2016Article
- Incidence, Predictors, and Impact on Hospital Mortality of Amphotericin B Nephrotoxicity Defined Using Newer Acute Kidney Injury Diagnostic Criteria.Antimicrobial agents and chemotherapy · 2015Article
- Long open amphotericin channels revealed in cholesterol-containing phospholipid membranes are blocked by thiazole derivative.The Journal of membrane biology · 2014Article
- An optimized nanoparticle delivery system based on chitosan and chondroitin sulfate molecules reduces the toxicity of amphotericin B and is effective in treating tegumentary leishmaniasis.International journal of nanomedicine · 2014Article
- Pathophysiology of acute kidney injury.Comprehensive Physiology · 2012Review
- It only takes one to do many jobs: Amphotericin B as antifungal and immunomodulatory drug.Frontiers in microbiology · 2012Article
- Amphotericin B membrane action: role for two types of ion channels in eliciting cell survival and lethal effects.The Journal of membrane biology · 2010Review
- A phospholipid-apolipoprotein A-I nanoparticle containing amphotericin B as a drug delivery platform with cell membrane protective properties.International journal of pharmaceutics · 2010Article
- Ischemic kidney injury and mechanisms of tissue repair.Wiley interdisciplinary reviews. Systems biology and medicineReview
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amphotericin B (AMB) is one of the most effective antifungal agents; however, its use is often limited by the occurrence of adverse events, especially nephrotoxicity. The present study was designed to determine the possible mechanisms underlying the nephrotoxic action of AMB. The exposure of a porcine proximal renal tubular cell line (LLC-PK1 cells) to AMB caused cell injury, as assessed by mitochondrial enzyme activity, the leakage of lactate dehydrogenase, and tissue ATP depletion. Propidium iodide uptake was enhanced, while terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was not affected by AMB, suggesting a lack of involvement of apoptosis in AMB-induced cell injury. The cell injury was inhibited by the depletion of membrane cholesterol with methyl-beta-cyclodextrin, which lowered the extracellular Na(+) concentration or the chelation of intracellular Ca(2+). The rise in the intracellular Ca(2+) concentration may be mediated through the activation of the ryanodine receptor (RyR) on the endoplasmic reticulum and the mitochondrial Na(+)-Ca(2+) exchanger, since cell injury was attenuated by dantrolene (an RyR antagonist) and CGP37157 (an Na(+)-Ca(2+) exchanger inhibitor). Moreover, AMB-induced cell injury was reversed by PD169316 (a p38 mitogen-activated protein [MAP] kinase inhibitor), c-Jun N-terminal kinase inhibitor II, and PD98059 (a MEK1/2 inhibitor). The phosphorylations of these MAP kinases were enhanced by AMB in a calcium-independent manner, suggesting the involvement of MAP kinases in AMB-induced cell injury. These findings suggest that Na(+) entry through membrane pores formed by the association of AMB with membrane cholesterol leads to the activation of MAP kinases and the elevation of the intracellular Ca(2+) concentration, leading to renal tubular cell injury.
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