Quercetin reduces hydroxyurea induced cytotoxicity in immortalized mouse aortic endothelial cells

PeerJ

article

Zachary M. Kiser¹  Monica D.M. McGee²  Racquel J. Wright³  Alexander Quarshie⁴  Gale W. Newman¹  Karen R. Randall⁵  Jonathan K. Stiles¹  Adel Driss⁶  Jacqueline M. Hibbert¹ 

[1] Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine;Spelman College;Biotechnology Centre, University of the West Indies;Community Health & Preventive Medicine, Morehouse School of Medicine;Department of Pharmacology & Toxicology, Morehouse School of Medicine;Department of Physiology, Morehouse School of Medicine

关键词: Quercetin;    Hydroxyurea;    Sickle cell disease;    Vascular endothelial cells;   

DOI  :  10.7717/peerj.3376

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundChronic 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.MethodsLipopolysaccharide (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.ResultsLDH 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).DiscussionThese 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.

【 授权许可】

CC BY