| Contribution of reactive oxygen species to para-aminophenol toxicity in LLC-PK1 cells. | |
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MedLine Citation:
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PMID: 18396305 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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para-aminophenol (PAP) causes nephrotoxicity by biochemical mechanisms that have not been fully elucidated. PAP can undergo enzymatic or non-enzymatic oxidation to form reactive intermediates. Using modulators of reactive oxygen species (ROS), the role of ROS in PAP toxicity in LLC-PK(1) cells was investigated. ROS formation was determined using a fluorescein derivative and viability using alamarBlue. Following treatment of cells with PAP, ROS formation occurred prior to loss of cell viability. Several modulators of ROS were used to identify the pathways involved in PAP toxicity. Viability was improved with catalase treatment, while viability was decreased when cells were treated with superoxide dismutase (SOD). Both catalase and SOD exert their effects outside of cells in the incubation medium, since there was no evidence of uptake of these enzymes in LLC-PK(1) cells. In cell-free incubations, hydrogen peroxide (H(2)O(2)) was produced when 0.5 mM PAP was included in the incubation medium. Further, SOD greatly increased and catalase greatly decreased H(2)O(2) production in these cell-free incubations. These data suggest that H(2)O(2) formed in the incubation medium contributes to loss of viability following PAP treatment. When cells were coincubated with 0.5 mM PAP and tiron, pyruvate, bathocuproine, 1, 10-phenanthroline, or dimethylthiourea (DMTU), ROS formation was decreased. However, there was minimal improvement in cell viability. Paradoxically, DMTU exacerbated PAP-induced loss of viability. These data suggest that ROS are generated in cells exposed to PAP but these species are not the predominant cause of cellular injury. |
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Authors:
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Brooke D Foreman; Joan B Tarloff |
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Publication Detail:
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Type: Journal Article Date: 2008-03-04 |
Journal Detail:
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Title: Toxicology and applied pharmacology Volume: 230 ISSN: 0041-008X ISO Abbreviation: Toxicol. Appl. Pharmacol. Publication Date: 2008 Jul |
Date Detail:
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Created Date: 2008-06-23 Completed Date: 2008-07-22 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0416575 Medline TA: Toxicol Appl Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 144-9 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, Philadelphia, PA 19104, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt Aminophenols / toxicity* Animals Antioxidants / metabolism Blotting, Western Catalase / metabolism Cell Survival / physiology Chelating Agents / pharmacology Electrophoresis, Polyacrylamide Gel Hydrogen Peroxide / metabolism LLC-PK1 Cells Oxidative Stress Pyruvic Acid / metabolism Reactive Oxygen Species / metabolism* Superoxide Dismutase / metabolism Swine |
| Grant Support | |
ID/Acronym/Agency:
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R15 GM065196-01A1/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Aminophenols; 0/Antioxidants; 0/Chelating Agents; 0/Reactive Oxygen Species; 123-30-8/4-aminophenol; 127-17-3/Pyruvic Acid; 149-45-1/1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; 7722-84-1/Hydrogen Peroxide; EC 1.11.1.6/Catalase; EC 1.15.1.1/Superoxide Dismutase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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