Safaeian Leila, Shafiee Fatemeh, Naderi Marzieh
Department of Pharmacology and Toxicology, Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Int J Prev Med. 2022 Feb 8;13:20. doi: 10.4103/ijpvm.IJPVM_425_20. eCollection 2022.
Oxidative stress has a prominent role in the pathogenesis of diabetes complications. Pramlintide is an injectional amylin analogue used for the treatment of type 1 and type 2 diabetic patients. The present investigation evaluated the effect of pramlintide against oxidative damage induced by hydrogen peroxide (HO) in human umbilical vein endothelial cells (HUVECs).
Cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Hydroperoxides level, ferric reducing antioxidant power (FRAP), and expression of transcription factor NF-κB were measured in HUVECs that pretreated with pramlintide and, then exposed to HO.
Pramlintide significantly decreased the cytotoxicity caused by HO at the concentrations of 5 and 10 μg/mL. Pretreatment of HUVECs with pramlintide reduced hydroperoxides and increased FRAP value in intra- and extra-cellular mediums at different concentration ranges compared with HO stimulated cells. Pramlintide (10 μg/mL) remarkably ameliorated the expression of NF-κB gene after 1, 3 and 24 h exposure to HO.
Findings of the current investigation displayed that pramlintide may act as a protective against oxidative conditions in endothelial cells through modulation of oxidative markers and transcription factor NF-κB.
氧化应激在糖尿病并发症的发病机制中起重要作用。普兰林肽是一种用于治疗1型和2型糖尿病患者的注射用胰淀素类似物。本研究评估了普兰林肽对过氧化氢(H₂O₂)诱导的人脐静脉内皮细胞(HUVECs)氧化损伤的影响。
采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐法评估细胞活力。在预先用普兰林肽处理然后暴露于H₂O₂的HUVECs中测量氢过氧化物水平、铁还原抗氧化能力(FRAP)和转录因子NF-κB的表达。
普兰林肽在5和10μg/mL浓度下显著降低了H₂O₂引起的细胞毒性。与H₂O₂刺激的细胞相比,用普兰林肽预处理HUVECs在不同浓度范围内降低了细胞内和细胞外培养基中的氢过氧化物并增加了FRAP值。在暴露于H₂O₂ 1、3和24小时后,普兰林肽(10μg/mL)显著改善了NF-κB基因的表达。
本研究结果表明,普兰林肽可能通过调节氧化标志物和转录因子NF-κB对内皮细胞的氧化状态起到保护作用。