Drug Design, Development and Therapy (Nov 2020)
Loxoprofen Sodium Alleviates Oxidative Stress and Apoptosis Induced by Angiotensin II in Human Umbilical Vein Endothelial Cells (HUVECs)
Abstract
Chuanzhao Ji,1 Yang Yu,2 Min Zhang,2 Wenyan Yu,2 Shuo Dong1 1Department of Cardiovascular Medicine Ward 2, Zibo Central Hospital, Zibo, Shandong 255020, People’s Republic of China; 2General Medicine Department of Zibo Central Hospital, Zibo, Shandong 255020, People’s Republic of ChinaCorrespondence: Shuo DongDepartment of Cardiovascular Medicine Ward 2, Zibo Central Hospital, No. 54, Gongqingtuan West Road, Zhangdian District, Zibo, Shandong 255020, People’s Republic of ChinaTel/Fax +86-0533-3179175Email [email protected] and Purpose: Endothelium exerts an important role in releasing vasoactive substances, maintaining the blood flow, regulating the growth of vessels, moderating the process of coagulation, and the balance of fibrinolytic system, the dysfunction of which is reported to result in arterial stiffness. The present study aimed to investigate the effects of loxoprofen sodium against HUVECs injury induced by angiotensin II.Methods: The injury model on HUVECs was established through incubation with angiotensin II. The expression levels of AT2R, NOX-4, Bax, Bcl-2, and caspase-3 were evaluated using qRT-PCR and Western Blot. DCFH-DA assay was used to detect the production of ROS and ELISA assay was used to evaluate the level of reduced glutathione. Mitochondrial membrane potential (MMP) was measured using dihydrorhodamine 123 assay. MTT and LDH assays were utilized to determine the proliferation ability of HUVECs. The apoptosis rate of HUVECs was evaluated using flow cytometry.Results: Loxoprofen sodium suppressed endothelial AT2R elevation by angiotensin II. Loxoprofen ameliorated Angiotensin II–induced production of ROS, reduced GSH, and NOX-2 and NOX-4 expression. Furthermore, Loxoprofen mitigated Angiotensin II, reduced mitochondrial membrane potential and improved cell viability, and suppressed LDH release by angiotensin II. Importantly, loxoprofen showed a beneficial role in protecting endothelial apoptosis by mitigating apoptotic machinery including the balanced expression of Bax, Bcl-2, and caspase-3 cleavage.Conclusion: Loxoprofen sodium might alleviate the high ROS levels and apoptosis induced by angiotensin II in HUVECs.Keywords: angiotensin II, apoptosis, endothelial cells, ROS
