Quercetin reduces hydroxyurea induced cytotoxicity in immortalized mouse aortic endothelial cells
Background Chronic inflammation is a characteristic of sickle cell disease (SCD), and is invariably associated with vascular endothelial injury. Hydroxyurea (HU), a naturally cytotoxic chemotherapeutic agent, is the only FDA drug approved for SCD, and is therefore naturally cytotoxic. Quercetin (QCT...
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PeerJ Inc.
2017-05-01
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| author | Zachary M. Kiser Monica D.M. McGee Racquel J. Wright Alexander Quarshie Gale W. Newman Karen R. Randall Jonathan K. Stiles Adel Driss Jacqueline M. Hibbert |
| author_facet | Zachary M. Kiser Monica D.M. McGee Racquel J. Wright Alexander Quarshie Gale W. Newman Karen R. Randall Jonathan K. Stiles Adel Driss Jacqueline M. Hibbert |
| author_sort | Zachary M. Kiser |
| collection | DOAJ |
| description | Background Chronic inflammation is a characteristic of sickle cell disease (SCD), and is invariably associated with vascular endothelial injury. Hydroxyurea (HU), a naturally cytotoxic chemotherapeutic agent, is the only FDA drug approved for SCD, and is therefore naturally cytotoxic. Quercetin (QCT) is a dietary flavonoid found ubiquitously in plants and foods that have anti-oxidative and anti-inflammatory characteristics. Our hypothesis is that dietary QCT will decrease cytotoxic effects of lipopolysaccharide (LPS) and HU induced vascular cell damage. Methods Lipopolysaccharide (LPS) was used to induce inflammation in immortalized mouse aortic endothelial cells (iMAECs), providing an in vitro model of inflamed endothelial cells. The cells were exposed to LPS throughout the entire experiment. Interventions included treating the LPS exposed cells with QCT, HU, or QCT + HU over 50 hours. The 50-hour period included 24 hours of varying treatments, followed by two hours of hypoxic exposure and then 24 hours under normal aerobic exposure. Results LDH level was significantly higher for LPS treated versus untreated cells (P = 0.0004). LPS plus 30 micromole QCT reduced the LDH (p = 0.1, trend), whereas LPS plus 100 micromoles HU, significantly increased LDH (p = 0.0004). However, LPS plus treatment with 30 micromoles QCT/100 micromoles HU, significantly reduced LDH, compared with HU alone (p = 0.0002). Discussion These results suggest that quercetin may be effective against vascular endothelial cell damage for iMAECs in vitro. In particular, it shows promise in preventing HU-induced cytotoxicity, surprisingly found from these results. This latter finding is important, and should be given more consideration, since HU is the only FDA-approved drug for treating sickle cell patients, and its use is rapidly increasing. |
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| last_indexed | 2024-03-09T07:02:34Z |
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| spelling | doaj.art-cc46985c91054aef9ff8c02f97e30b042023-12-03T09:50:12ZengPeerJ Inc.PeerJ2167-83592017-05-015e337610.7717/peerj.3376Quercetin reduces hydroxyurea induced cytotoxicity in immortalized mouse aortic endothelial cellsZachary M. Kiser0Monica D.M. McGee1Racquel J. Wright2Alexander Quarshie3Gale W. Newman4Karen R. Randall5Jonathan K. Stiles6Adel Driss7Jacqueline M. Hibbert8Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA, United States of AmericaSpelman College, Atlanta, GA, United States of AmericaBiotechnology Centre, University of the West Indies, Mona, JamaicaCommunity Health & Preventive Medicine, Morehouse School of Medicine, Atlanta, GA, United States of AmericaDepartment of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA, United States of AmericaDepartment of Pharmacology & Toxicology, Morehouse School of Medicine, Atlanta, GA, United States of AmericaDepartment of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA, United States of AmericaDepartment of Physiology, Morehouse School of Medicine, Atlanta, GA, United States of AmericaDepartment of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA, United States of AmericaBackground Chronic inflammation is a characteristic of sickle cell disease (SCD), and is invariably associated with vascular endothelial injury. Hydroxyurea (HU), a naturally cytotoxic chemotherapeutic agent, is the only FDA drug approved for SCD, and is therefore naturally cytotoxic. Quercetin (QCT) is a dietary flavonoid found ubiquitously in plants and foods that have anti-oxidative and anti-inflammatory characteristics. Our hypothesis is that dietary QCT will decrease cytotoxic effects of lipopolysaccharide (LPS) and HU induced vascular cell damage. Methods Lipopolysaccharide (LPS) was used to induce inflammation in immortalized mouse aortic endothelial cells (iMAECs), providing an in vitro model of inflamed endothelial cells. The cells were exposed to LPS throughout the entire experiment. Interventions included treating the LPS exposed cells with QCT, HU, or QCT + HU over 50 hours. The 50-hour period included 24 hours of varying treatments, followed by two hours of hypoxic exposure and then 24 hours under normal aerobic exposure. Results LDH level was significantly higher for LPS treated versus untreated cells (P = 0.0004). LPS plus 30 micromole QCT reduced the LDH (p = 0.1, trend), whereas LPS plus 100 micromoles HU, significantly increased LDH (p = 0.0004). However, LPS plus treatment with 30 micromoles QCT/100 micromoles HU, significantly reduced LDH, compared with HU alone (p = 0.0002). Discussion These results suggest that quercetin may be effective against vascular endothelial cell damage for iMAECs in vitro. In particular, it shows promise in preventing HU-induced cytotoxicity, surprisingly found from these results. This latter finding is important, and should be given more consideration, since HU is the only FDA-approved drug for treating sickle cell patients, and its use is rapidly increasing.https://peerj.com/articles/3376.pdfQuercetinHydroxyureaSickle cell diseaseVascular endothelial cells |
| spellingShingle | Zachary M. Kiser Monica D.M. McGee Racquel J. Wright Alexander Quarshie Gale W. Newman Karen R. Randall Jonathan K. Stiles Adel Driss Jacqueline M. Hibbert Quercetin reduces hydroxyurea induced cytotoxicity in immortalized mouse aortic endothelial cells PeerJ Quercetin Hydroxyurea Sickle cell disease Vascular endothelial cells |
| title | Quercetin reduces hydroxyurea induced cytotoxicity in immortalized mouse aortic endothelial cells |
| title_full | Quercetin reduces hydroxyurea induced cytotoxicity in immortalized mouse aortic endothelial cells |
| title_fullStr | Quercetin reduces hydroxyurea induced cytotoxicity in immortalized mouse aortic endothelial cells |
| title_full_unstemmed | Quercetin reduces hydroxyurea induced cytotoxicity in immortalized mouse aortic endothelial cells |
| title_short | Quercetin reduces hydroxyurea induced cytotoxicity in immortalized mouse aortic endothelial cells |
| title_sort | quercetin reduces hydroxyurea induced cytotoxicity in immortalized mouse aortic endothelial cells |
| topic | Quercetin Hydroxyurea Sickle cell disease Vascular endothelial cells |
| url | https://peerj.com/articles/3376.pdf |
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