The effect of N-acetyl cysteine on H2O2 mediated oxidative stress in Whartonʼs jelly derived mesenchymal stem cells

Fatima Ali, Abdu Ur Rehman Qadir, Nishat Fatima, Nadia Wajid

Abstract


Background: Hypoxic stress is a crucial factor for retaining the cell survival in injured tissue. Overcoming this issue is the key for successful cellular regenerative therapy. Therefore the purpose of this study was to investigate whether the in-vitro pretreatment of Whartonʼs Jelly (WJ) derived Mesenchymal stem cells (WJ-MSCs) with an antioxidant, namely N-acetylcysteine (NAC), can improve the efficacy of WJ-MSCs for transplantation purpose.

Methods: WJ-MSCs were cultured with or without NAC at different concentrations (0.1mM, 1mM and 10mM). To simulate oxidative stress conditions, cultures were exposed to hydrogen peroxide (H2O2) 100 µM for 1 hour. Cytoprotective effect of NAC was evaluated by determining cell injury, viability, and proliferation. The oxidative stress is assessed by measuring the activity of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and malodialdehyde (MDA).

Results: Pretreatment of WJ-MSCs with NAC increased their viability and proliferation in concentration-dependent manner. Furthermore, 10 mM NAC significantly reduced the H2Oinduced oxidative stress by enhancing the activity of GSH, SOD, and CAT and reduced the level of MDA

Conclusion: The study results indicate that NAC may abrogate H2O2 induced oxidative-stress of WJ-MSCs. This study provides basis to explore NAC effect on WJ-MSCs survival without cytotoxicity.


Full Text:

PDF

References


Kim DW, Staples M, Shinozuka K, Pantcheva P, Kang SD, Borlongan CV. Wharton's jelly-derived mesenchymal stem cells: phenotypic characterization and optimizing their therapeutic potential for clinical applications. Int J Mol Sci, (2013); 14(6):11692-712.

Khan M, Ali F, Mohsin S, Akhtar S, Mehmood A, Choudhery MS. Khan SN, Riazuddin S. Preconditioning diabetic mesenchymal stem cells with myogenic medium increases their ability to repair diabetic heart. Stem Cell Res Ther, (2013); 4(3):58.

Saini U, Gumina RJ, Wolfe B, Kuppusamy ML, Kuppusamy P, Boudoulas KD. Preconditioning mesenchymal stem cells with caspase inhibition and hyperoxia prior to hypoxia exposure increases cell proliferation. J Cell Biochem, (2013); 114(11):2612-23.

Ali F, Khan M,Khan SN, Riazuddin S. N-Acetyl cysteine protects diabetic mouse derived mesenchymal stem cells from H2O2 induced injury:A novel hypothesis for autologous stem cells transplantation. Journal of the Chinese Medical Association, doi.10.1016/j.jcma.2015.09.005.

Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res, (2010); 107(9):1058-70.

Poljsak B, Suput D, Milisav I. Achieving the balance between ROS and antioxidants: when to use the synthetic antioxidants. Oxid Med Cell Longev, (2013);2013:956792.

Bavarsad Shahripour R, Harrigan MR, Alexandrov AV. N-acetylcysteine (NAC) in neurological disorders: mechanisms of action and therapeutic opportunities. Brain Behav, (2014); 4(2):108-22.

Xie J, Zhou X, Hu X, Jiang H. H2O2 evokes injury of cardiomyocytes through upregulating HMGB1. Hellenic J Cardiol, (2014) ;55(2):101-6.

Sun Y, Pu LY, Lu L, Wang XH, Zhang F, Rao JH. N-acetylcysteine attenuates reactive-oxygen-species-mediated endoplasmic reticulum stress during liver ischemia-reperfusion injury. World J Gastroenterol, (2014); 20(41):15289-98.

Wajid N, Naseem R, Anwar SS, Awan SJ, Ali M, Javed S, Ali F. The effect of gestational diabetes on proliferation capacity and viability of human umbilical cord-derived stromal cells. Cell Tissue Bank, (2015); 16(3):389-97.

Ali F, Naqvi SA S, Bismillah M, Wajid N. Comparative analysis of biochemical parameters in diabetic and non-diabetic acute myocardial infarction patients. Indian Heart Journal, (2016); DOI: 10.1016/j.ihj.2015.09.026.

Sung CC, Hsu YC, Chen CC, Lin YF, Wu CC. Oxidative stress and nucleic acid oxidation in patients with chronic kidney disease. Oxid Med Cell Longev, (2013);2013:301982.

Ansley DM, Wang B. Oxidative stress and myocardial injury in the diabetic heart. J Pathol, (2013); 229(2):232-41.

Mennan C, Wright K, Bhattacharjee A, Balain B, Richardson J, Roberts S. Isolation and characterisation of mesenchymal stem cells from different regions of the human umbilical cord. Biomed Res Int, (2013); 2013:916136.

Barachini S, Trombi L, Danti S. Morpho-functional characterization of human mesenchymal stem cells from umbilical cord blood for potential uses in regenerative medicine. Stem Cells Dev, (2009);18(2): 293-305.

Ali F, Rafique H, Wajid N. N-acetylcysteine prevents cord derived stem cells from H2O2 induced injury in vitro. EJPMR, (2015); 2(3), 589-598.

Yu SP, Wei Z, Wei L. Preconditioning strategy in stem cell transplantation therapy. Transl Stroke Res, (2013); 4(1):76-88.

Haider HKh, Ashraf M. Strategies to promote donor cell survival: combining preconditioning approach with stem cell transplantation. J Mol Cell Cardiol, (2008); 45(4):554-66.

Li CJ, Sun LY, Pang CY. Synergistic protection of N-acetylcysteine and ascorbic acid 2-phosphate on human mesenchymal stem cells against mitoptosis, necroptosis and apoptosis. Sci Rep, (2015);5:9819.

Li P, Li Z. Neuroprotective effect of paeoniflorin on H2O2-induced apoptosis in PC12 cells by modulation of reactive oxygen species and the inflammatory response. Exp Ther Med, (2015); 9(5):1768-1772.

Wisel S, Khan M, Kuppusamy ML, Mohan IK, Chacko SM, Rivera BK, Sun BC, Hideg K, Kuppusamy P. Pharmacological preconditioning of mesenchymal stem cells with trimetazidine (1-[2,3,4-trimethoxybenzyl]piperazine) protects hypoxic cells against oxidative stress and enhances recovery of myocardial function in infarcted heart through Bcl-2 expression. J Pharmacol Exp Ther, (2009); 329(2):543-50.

Frank J, Pompella A, Biesalski HK. Histochemical visualization of oxidant stress. Free Radic Biol Med, (2000); 29(11):1096-105.

Deavall DG, Martin EA, Horner JM, Roberts R. Drug-induced oxidative stress and toxicity. J Toxico, (2012); 2012: 645460.

Rahman K. Studies on free radicals, antioxidants, and co-factors. Clin Interv Aging, (2007); 2(2):219-36.


Refbacks

  • There are currently no refbacks.