Mehdi Hassanpour
1,2 
, Çıgır Biray Avci
3 , Reza Rahbarghazi
1,4* , Aysa Rezabakhsh
5 , Alireza Nourazarian
2 , Elahe Nabat
1, Farzaneh Fathi
6 , Majid Khaksar
11 Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2 Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
3 Department of Medical Biology, Faculty of Medicine, Ege University, Izmir, Turkey
4 Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
5 Cardiovascular Research Center, Tabriz University of Medical Science, Tabriz, Iran
6 Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
Abstract
Introduction: According to the statistics, vascular injury occurs during the onset of diabetic changes after the production of several byproducts. Many authorities have focused to find an alternative therapy for diabetic patients. In this study, we investigated the therapeutic effects of natural polyphenol like resveratrol on human endothelial cells exposed to malondialdehyde for 48 hours.
Methods: Human Umbilical Vein Endothelial Cells were randomly classified into four groups;control, malondialdehyde (2.5 mM), resveratrol (100 μM), and cells received the combined regime for 48 hours. Cell viability was determined by 3-(4, 5-dimethyl thiazol-2-yl) 2, 5-diphenyl-tetrazoliumbromide (MTT) assay. Griess reaction was performed to measure the content of Nitric oxide (NO).Apoptosis was studied by using real-time polymerase chain reaction (RT-PCR) and western blotting assays. Levels of receptor tyrosine kinases like VEGFR-1, -2, Tie-1, and -2 were analyzed by enzyme-linked immunosorbent assay(ELISA). The affinity of resveratrol and malondialdehyde to serum albumin was measured by Surface Plasmon Resonance Assay. Any changes in chromatin remodeling were detected by PCR array analysis.
Results: Resveratrol reduced cytotoxicity and NO content inside cells induced by malondialdehyde(MDA) (P < 0.05). Endothelial cell apoptosis was decreased by the reduction of pro-apoptotic factor Bax and increase of Bcl-2 following the incubation with resveratrol (P < 0.05). MDA-induced receptor tyrosine kinases increase was inhibited by resveratrol and reached near-to-normal levels (P < 0.05).Surface Plasmon Resonance revealed a higher affinity of resveratrol to albumin compared to the malondialdehyde-albumin complex. Polymerase chain reaction (PCR) array revealed the potency of resveratrol in chromatin remodeling following the treatment with malondialdehyde (P < 0.05).
Conclusion: Based on our findings, resveratrol has the potential to decrease diabetic vascular injury induced by lipid byproducts such as MDA.