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Effect of MRSA on CYP450: dynamic changes of cytokines, oxidative stress, and drug-metabolizing enzymes in mice infected with MRSA
BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a very damaging and widespread pathogen, which is associated with many diseases and causes serious infections. MRSA infection can modulate the effects of drugs, which may occur through an influence on cytochrome P450 (CYP450), the dru...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5815478/ https://www.ncbi.nlm.nih.gov/pubmed/29491713 http://dx.doi.org/10.2147/IDR.S153871 |
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author | Tang, Huaqiao Long, Nana Lin, Lin Liu, Yao Li, Jianlong Sun, Fenghui Guo, Lijuan Zhang, Fen Dai, Min |
author_facet | Tang, Huaqiao Long, Nana Lin, Lin Liu, Yao Li, Jianlong Sun, Fenghui Guo, Lijuan Zhang, Fen Dai, Min |
author_sort | Tang, Huaqiao |
collection | PubMed |
description | BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a very damaging and widespread pathogen, which is associated with many diseases and causes serious infections. MRSA infection can modulate the effects of drugs, which may occur through an influence on cytochrome P450 (CYP450), the drug-metabolizing enzyme in the liver. In this study, we evaluated the underlying mechanism of drug failure or poisoning in MRSA infection. MATERIALS AND METHODS: Mice were infected with three different doses of MRSA and the changes in CYP450 expression, cytokines, and oxidative stress markers were evaluated. RESULTS: The administration of an attack dose of MRSA caused serious symptoms of infection and resulted in a 40% mortality rate in the mice. MRSA induced strong inflammation and oxidative stress in the mice, predominantly caused by significant increases in interleukin (IL)-1β, IL-4, IL-6, macrophage inflammatory protein, glutathione S-transferase (GST), and malondialdehyde, and decreases in oxygen radical absorbance capacity and glutathione levels in the liver. The expression of IL-2, tumor necrosis factor-α, and GST was briefly suppressed, but increased on days 3 and 7. The increased inflammation and oxidative stress further induced a significant decrease in the mRNA levels and activities of CYP450 1A2, 2D22, 2E1, and 3A1 in MRSA-infected mice within the first day of infection. CONCLUSION: These results show that MRSA infection leads to inflammation and oxidative stress, and reduces the expression levels and activities of drug metabolism enzymes, which decreased drug metabolism in patients infected with MRSA. Therefore, to avoid a drug overdose, the plasma concentration of patients with MRSA infection should be continuously monitored. |
format | Online Article Text |
id | pubmed-5815478 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-58154782018-02-28 Effect of MRSA on CYP450: dynamic changes of cytokines, oxidative stress, and drug-metabolizing enzymes in mice infected with MRSA Tang, Huaqiao Long, Nana Lin, Lin Liu, Yao Li, Jianlong Sun, Fenghui Guo, Lijuan Zhang, Fen Dai, Min Infect Drug Resist Original Research BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a very damaging and widespread pathogen, which is associated with many diseases and causes serious infections. MRSA infection can modulate the effects of drugs, which may occur through an influence on cytochrome P450 (CYP450), the drug-metabolizing enzyme in the liver. In this study, we evaluated the underlying mechanism of drug failure or poisoning in MRSA infection. MATERIALS AND METHODS: Mice were infected with three different doses of MRSA and the changes in CYP450 expression, cytokines, and oxidative stress markers were evaluated. RESULTS: The administration of an attack dose of MRSA caused serious symptoms of infection and resulted in a 40% mortality rate in the mice. MRSA induced strong inflammation and oxidative stress in the mice, predominantly caused by significant increases in interleukin (IL)-1β, IL-4, IL-6, macrophage inflammatory protein, glutathione S-transferase (GST), and malondialdehyde, and decreases in oxygen radical absorbance capacity and glutathione levels in the liver. The expression of IL-2, tumor necrosis factor-α, and GST was briefly suppressed, but increased on days 3 and 7. The increased inflammation and oxidative stress further induced a significant decrease in the mRNA levels and activities of CYP450 1A2, 2D22, 2E1, and 3A1 in MRSA-infected mice within the first day of infection. CONCLUSION: These results show that MRSA infection leads to inflammation and oxidative stress, and reduces the expression levels and activities of drug metabolism enzymes, which decreased drug metabolism in patients infected with MRSA. Therefore, to avoid a drug overdose, the plasma concentration of patients with MRSA infection should be continuously monitored. Dove Medical Press 2018-02-13 /pmc/articles/PMC5815478/ /pubmed/29491713 http://dx.doi.org/10.2147/IDR.S153871 Text en © 2018 Tang et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Tang, Huaqiao Long, Nana Lin, Lin Liu, Yao Li, Jianlong Sun, Fenghui Guo, Lijuan Zhang, Fen Dai, Min Effect of MRSA on CYP450: dynamic changes of cytokines, oxidative stress, and drug-metabolizing enzymes in mice infected with MRSA |
title | Effect of MRSA on CYP450: dynamic changes of cytokines, oxidative stress, and drug-metabolizing enzymes in mice infected with MRSA |
title_full | Effect of MRSA on CYP450: dynamic changes of cytokines, oxidative stress, and drug-metabolizing enzymes in mice infected with MRSA |
title_fullStr | Effect of MRSA on CYP450: dynamic changes of cytokines, oxidative stress, and drug-metabolizing enzymes in mice infected with MRSA |
title_full_unstemmed | Effect of MRSA on CYP450: dynamic changes of cytokines, oxidative stress, and drug-metabolizing enzymes in mice infected with MRSA |
title_short | Effect of MRSA on CYP450: dynamic changes of cytokines, oxidative stress, and drug-metabolizing enzymes in mice infected with MRSA |
title_sort | effect of mrsa on cyp450: dynamic changes of cytokines, oxidative stress, and drug-metabolizing enzymes in mice infected with mrsa |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5815478/ https://www.ncbi.nlm.nih.gov/pubmed/29491713 http://dx.doi.org/10.2147/IDR.S153871 |
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