Potential Toxicity of Polymyxins in Human Lung Epithelial Cells
Maizbha U Ahmed, Tony Velkov, Yu-Wei Lin, Bo Yun, Cameron J Nowell, Fanfan Zhou, Qi Tony Zhou, Kim Chan, Mohammad AK Azad, Jian Li
Antimicrobial Agents and Chemotherapy | AMER SOC MICROBIOLOGY | Published : 2017
Inhaled polymyxins are of considerable utility in achieving optimal exposure in the respiratory tract for the treatment of lung infections caused by multidrug-resistant Gram-negative pathogens. Current inhaled polymyxin therapy is empirical, and often large doses are used that may lead to potential pulmonary adverse effects. This study aimed to investigate the effect of polymyxins on human lung epithelial (A549) cells. The viability of A549 cells was examined after treatment with polymyxins by flow cytometry. Activation of caspases 3, 8, and 9, expression of Fas ligand (FasL), loss of mitochondrial membrane potential, and mitochondrial oxidative stress induced by polymyxin B were evaluated. ..View full abstract
Awarded by Australian National Health and Medical Research Council (NHMRC)
Awarded by National Institute of Allergy and Infectious Diseases of the National Institutes of Health
Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
J.L., F.Z., Q.T.Z., K.C., and T.V. are supported by the Australian National Health and Medical Research Council (NHMRC; ID 1104581). J.L. is an NHMRC senior research fellow, and T.V. is an NHMRC career development fellow. J.L. and T.V. are also supported by a research grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (R01 AI111965). The content of this report is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. M.U.A. is supported by a Monash Graduate Scholarship and a Stan Robson Rural Pharmacy Equity Scholarship.