| Development of an albuminous reactive oxygen species assay for photosafety evaluation under experimental biomimetic conditions. | |
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MedLine Citation:
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PMID: 23355082 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The generation of reactive oxygen species (ROS) from an ultraviolet (UV)-exposed chemical can be an experimental indicator of phototoxic potential. The aim of the present study was to develop a new ROS assay using serum albumin to provide photosafety assessment under experimental biomimetic conditions. To assess assay robustness, a validation study on an albuminous ROS (aROS) assay was conducted with a focus on intra- and inter-day precisions and Z'-factor reflecting both the assay signal-to-noise ratio and variation associated with signal measurements. In the aROS assay on quinine HCl (200 µM), a typical phototoxic drug, both intra- and inter-day precisions (coefficient of variation; CV) were found to be below 4%, and the Z'-factors for singlet oxygen and superoxide suggested a large separation band between samples and blank signals. To evaluate the prediction capacity, the aROS and ROS assays were applied to 21 phototoxins and 10 non-phototoxic chemicals. Upon aROS assay on these model chemicals, the individual specificity was 100%, and the positive and negative predictivities were found to be 100% and 81.8%, respectively. The aROS assay can be employed for poorly soluble chemicals for which the ROS assay is unavailable. Comparing the ROS assay data, there seemed to be a photochemical transition of some chemicals in albuminous solution. A molecular interaction between albumin and chemical was also assessed by UV and fluorescent spectroscopic analyses, and the results suggested the limited relationship between the albumin-chemical interaction and the photochemical change. The aROS assay may allow photosafety assessment of new drug entities with a wide range of applicability partly under experimental biomimetic conditions. Copyright © 2013 John Wiley & Sons, Ltd. |
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Authors:
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Satomi Onoue; Masashi Kato; Shizuo Yamada |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-28 |
Journal Detail:
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Title: Journal of applied toxicology : JAT Volume: - ISSN: 1099-1263 ISO Abbreviation: J Appl Toxicol Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8109495 Medline TA: J Appl Toxicol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2013 John Wiley & Sons, Ltd. |
Affiliation:
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Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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