Significant accumulation of polymyxin in single renal tubular cells: a medicinal chemistry and triple correlative microscopy approach.
Anal Chem
; 87(3): 1590-5, 2015 Feb 03.
Article
en En
| MEDLINE
| ID: mdl-25553489
ABSTRACT
Polymyxin is the last-line therapy against Gram-negative 'superbugs'; however, dose-limiting nephrotoxicity can occur in up to 60% of patients after intravenous administration. Understanding the accumulation and concentration of polymyxin within renal tubular cells is essential for the development of novel strategies to ameliorate its nephrotoxicity and to develop safer, new polymyxins. We designed and synthesized a novel dual-modality iodine-labeled fluorescent probe for quantitative mapping of polymyxin in kidney proximal tubular cells. Measured by synchrotron X-ray fluorescence microscopy, polymyxin concentrations in single rat (NRK-52E) and human (HK-2) kidney tubular cells were approximately 1930- to 4760-fold higher than extracellular concentrations. Our study is the first to quantitatively measure the significant uptake of polymyxin in renal tubular cells and provides crucial information for the understanding of polymyxin-induced nephrotoxicity. Importantly, our approach represents a significant methodological advancement in determination of drug uptake for single-cell pharmacology.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Química Farmacéutica
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Sincrotrones
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Polimixinas
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Análisis de la Célula Individual
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Túbulos Renales
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Microscopía Fluorescente
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Antibacterianos
Límite:
Animals
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Humans
Idioma:
En
Revista:
Anal Chem
Año:
2015
Tipo del documento:
Article
País de afiliación:
Australia