[PMID]: | 28865757 |
[Au] Autor: | Menotti J; Alanio A; Sturny-Leclère A; Vitry S; Sauvage F; Barratt G; Bretagne S |
[Ad] Endereço: | Institut Pasteur, CNRS, Molecular Mycology unit, URA3012 Paris, France; Laboratory of Parasitology-Mycology, Saint-Louis Lariboisière Fernand Widal hospitals, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Paris-Diderot, Sorbonne Paris Cité University, Paris, France; Laboratory of Par |
[Ti] Título: | A cell impedance-based real-time in vitro assay to assess the toxicity of amphotericin B formulations. |
[So] Source: | Toxicol Appl Pharmacol;334:18-23, 2017 Nov 01. |
[Is] ISSN: | 1096-0333 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | Aerosolized liposomal amphotericin B (L-AmB) has been investigated as prophylaxis against invasive aspergillosis. However, the clinical results are controversial and some trials suggest that toxicity could be a limitation for wider use. Our aim was to assess the dynamics of cell toxicity induced in a human alveolar epithelial cell line (A549) after exposure to L-AmB (50 to 400µg/ml) or amphotericin B deoxycholate (D-AmB; 50 to 200µg/ml) by monitoring real-time A549 cell viability using an impedance-based technology. Results were expressed as cell index values integrating cell adhesion, proliferation, and survival. In parallel, the gene expression of proinflammatory cytokines was quantified at 6 and 24h after drug addition by real-time RT-PCR on cell lysates. No sustained reduction of cell indexes was observed with L-AmB or empty liposomes, even at 400µg/ml. Only the highest concentration tested of L-AmB (400µg/ml) yielded transient significant 6-fold and 4-fold induction of TNF-α and IL-8 mRNAs, respectively. In contrast, D-AmB induced a decrease in cell indexes and only the 50µg/ml concentration of D-AmB was followed by cell recovery, higher concentrations leading to cell death. Significant 4-fold, 7-fold and 3-fold inductions of TNF-α, IL-8 and IL-33 mRNAs were also observed at 6h with 50µg/ml of D-AmB. In conclusion, continuous cell impedance measurement showed no toxicity on overall cellular behavior although a slight proinflammatory cytokine expression is possible after L-AmB challenge. Real-time kinetics of cell impedance is an interesting tool for initial screening of cell toxicity. |
[Mh] Termos MeSH primário: |
Aerossóis/toxicidade Anfotericina B/toxicidade Antifúngicos/toxicidade Ácido Desoxicólico/toxicidade Impedância Elétrica Células Epiteliais/efeitos dos fármacos
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[Mh] Termos MeSH secundário: |
Células A549 Anfotericina B/química Antifúngicos/química Adesão Celular/efeitos dos fármacos Proliferação Celular/efeitos dos fármacos Sobrevivência Celular/efeitos dos fármacos Citocinas/genética Citocinas/metabolismo Formas de Dosagem Combinação de Medicamentos Regulação da Expressão Gênica/efeitos dos fármacos Seres Humanos
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Aerosols); 0 (Antifungal Agents); 0 (Cytokines); 0 (Dosage Forms); 0 (Drug Combinations); 0 (liposomal amphotericin B); 005990WHZZ (Deoxycholic Acid); 7XU7A7DROE (Amphotericin B); 87687-70-5 (amphotericin B, deoxycholate drug combination) |
[Em] Mês de entrada: | 1710 |
[Cu] Atualização por classe: | 171017 |
[Lr] Data última revisão:
| 171017 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170904 |
[St] Status: | MEDLINE |
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