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Potential for systemic pyocyanin-mediated toxicity.

Devinder Arora,Gary Grant,Rachel Morrison,Amelia J. McFarland,Susan Hall,Anoopkimar-Dukie, S+2 more-2014-01-01-Griffith Research Online (Griffith University, Queensland, Australia)
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Objectives: This study sought to investigate the diffusion of PCN\nthrough the pulmonary membrane and identify any potential barriers\nto diffusion. This was followed by studies of mice and human blood\nfollowing exposure to PCN. Materials and Methods: Permeability\nand metabolism were assessed in silica. C57BL/6J male mice were\ninoculated by intranasal route with 50μg PCN, and plasma levels were\ndetected by validated HPLC method. Open field and forced swimming\ntest were performed to assess the effect of PCN on mouse behaviour.\nPCN in CF patients chronically infected withP. aeruginosawas\ndetermined by HPLC. Results: This study found that PCN is readily\ndiffusible in silica in a concentration-pH-dependent manner. PCN was\nnot readily metabolised by CYP enzymes in silica and demonstrated\nto be NADP+ dependent. Significant levels of PCN were detected\nin mice plasma samples following short-term exposure, and in\nthe sputum of some samples from subjects chronically exposed to\nPCN p

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Objectives: This study sought to investigate the diffusion of PCN\nthrough the pulmonary membrane and identify any potential barriers\nto diffusion. This was followed by studies of mice and human blood\nfollowing exposure to PCN. Materials and Methods: Permeability\nand metabolism were assessed in silica. C57BL/6J male mice were\ninoculated by intranasal route with 50μg PCN, and plasma levels were\ndetected by validated HPLC method. Open field and forced swimming\ntest were performed to assess the effect of PCN on mouse behaviour.\nPCN in CF patients chronically infected withP. aeruginosawas\ndetermined by HPLC. Results: This study found that PCN is readily\ndiffusible in silica in a concentration-pH-dependent manner. PCN was\nnot readily metabolised by CYP enzymes in silica and demonstrated\nto be NADP+ dependent. Significant levels of PCN were detected\nin mice plasma samples following short-term exposure, and in\nthe sputum of some samples from subjects chronically exposed to\nPCN p

Keywords

PyocyaninCystic fibrosisChemistryPharmacologySystemic circulationToxicityHigh-performance liquid chromatographyMedicine

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