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Antimicrob Agents Chemother. 2013 Sep;57(9):4329-4335. doi: 10.1128/AAC.02587-12. Epub 2013 Jun 24.

Polymyxin B Induces Apoptosis in Kidney Proximal Tubular Cells.

Antimicrobial agents and chemotherapy

Mohammad A K Azad, Ben A Finnin, Anima Poudyal, Kathryn Davis, Jinhua Li, Prue A Hill, Roger L Nation, Tony Velkov, Jian Li

Affiliations

  1. Drug Delivery, Disposition and Dynamics.
  2. Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
  3. Department of Anatomy and Developmental Biology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.
  4. Department of Anatomical Pathology, St Vincent's Hospital, Fitzroy, Victoria, Australia.
  5. Drug Delivery, Disposition and Dynamics [email protected] [email protected].

PMID: 23796937 PMCID: PMC3754291 DOI: 10.1128/AAC.02587-12

Abstract

The nephrotoxicity of polymyxins is a major dose-limiting factor for treatment of infections caused by multidrug-resistant Gram-negative pathogens. The mechanism(s) of polymyxin-induced nephrotoxicity is not clear. This study aimed to investigate polymyxin B-induced apoptosis in kidney proximal tubular cells. Polymyxin B-induced apoptosis in NRK-52E cells was examined by caspase activation, DNA breakage, and translocation of membrane phosphatidylserine using Red-VAD-FMK [Val-Ala-Asp(O-Me) fluoromethyl ketone] staining, a terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, and double staining with annexin V-propidium iodide (PI). The concentration dependence (50% effective concentration [EC

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