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Bioimpacts. 2017;7(4): 219-226.
doi: 10.15171/bi.2017.26
PMID: 29435429
PMCID: PMC5801533
Scopus ID: 85040964888
  Abstract View: 3059
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Original Research

Effect of hydroxychloroquine on oxidative/nitrosative status and angiogenesis in endothelial cells under high glucose condition

Aysa Rezabakhsh 1,2, Soheila Montazersaheb 2,3, Elahe Nabat 2, Mehdi Hassanpour 4, Azadeh Montaseri 5, Hassan Malekinejad 6,7, Ali Akbar Movassaghpour 8, Reza Rahbarghazi 2,9*, Alireza Garjani 1,2*

1 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
2 Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
3 Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
4 Depatment of Clinical Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
5 Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
6 Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
7 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran
8 Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
9 Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
*Corresponding Authors: Email: rezarahbardvm@gmail.com; Email: garjania@tbzmed.ac.ir

Abstract

Introduction: Under the diabetic condition, sustained production of oxidative/nitrosative stress results in irreversible vascular injuries. A great number of diabetic pathologies, such as inefficient or aberrant neo-angiogenesis emerge following chronic hyperglycemic condition. Lack of enough data exists regarding hydroxychloroquine (HCQ) contribution on angiogenesis during diabetes mellitus.
Methods: To better address whether HCQ could blunt or exacerbate oxidative status and angiogenesis under high glucose condition (HCG), human umbilical vein endothelial cells (HUVECs) were exposed to 30 µM HCQ in combination with 30 mM glucose over a course of 72 hours. Viability was measured was evaluated by MTT assay. We used Griess method and TBARS assay to monitor changes in the levels of NO and MDA followed by flow cytometric analysis of ROS using DCFDA. To show the impact of HCQ on cell motility and in vitro angiogenic properties, we exploited routine scratch test and in vitro tubulogenesis, respectively.
Results: Our data showed that HCQ diminished cell viability under 5 and 30 mM glucose contents. HCQ significantly decreased the total levels of nitric oxide (NO), malondialdehyde (MDA), and reactive oxygen species (ROS) in both sets of environments. Additionally, inhibitory effects were observed on cell migration after exposure to HCQ (P < 0.001). Anti-angiogenic activity of HCQ was confirmed by the reduction of tube areas under a normal or surplus amount of glucose (P < 0.001).
Conclusion: In overall, results suggest that HCQ changes the oxidative/nitrosative status of HUVECs both in 5 and 30 mM conditions. HCQ is able to reduce migration and angiogenic activity of HUVECs irrespective of the glucose content.
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Submitted: 17 Sep 2016
Revision: 16 Jun 2017
Accepted: 20 Jun 2017
ePublished: 23 Aug 2017
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