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J Chin Med Assoc. 2016 Mar;79(3):122-9. doi: 10.1016/j.jcma.2015.09.005. Epub 2016 Feb 26.

N-Acetyl cysteine protects diabetic mouse derived mesenchymal stem cells from hydrogen-peroxide-induced injury: A novel hypothesis for autologous stem cell transplantation.

Author information

1
The University of Lahore, Defence Road Campus, Lahore, Pakistan; National Center of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan. Electronic address: Fatemei.ali@gmail.com.
2
National Center of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan; Center for Translational Medicine, Temple University, Lewis Katz School of Medicine, Philadelphia, PA, USA.
3
National Center of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
4
The University of Lahore, Defence Road Campus, Lahore, Pakistan; National Center of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan; Allama Iqbal Medical College/Jinnah Hospital Complex, University of Health Sciences, Lahore, Pakistan.

Abstract

BACKGROUND:

Stem cell transplantation is one of the therapeutic options available to repair damaged organs. However, transplanted cells entail several challenges including their survival in diabetes-affected injured tissue. This study was designed to determine the effects of preconditioning of mesenchymal stem cells (MSCs) with N-acetyl cysteine (NAC), a widely used antioxidant drug.

METHODS:

Diabetic-mouse-derived MSCs (blood glucose ≥ 300 mg/dL) were preconditioned with 30 mM NAC for 1 hour followed by oxidative injury with 100 μM hydrogen peroxide (H2O2) for 1 hour.

RESULTS:

Gene expression analysis showed marked upregulation of prosurvival genes (Akt and Bcl-2) and significantly downregulated expression of proapoptotic and stress genes (Capase-3, Bax, Bak, p53, p38, and NF-κB) in the 30 mM-NAC-treated group when compared with those cells treated with H2O2 alone. NAC preconditioning improved cell viability, decreased lactate dehydrogenase release, β-galactosidase activity, and Annexin-V-positive cells. Also, amelioration of oxidative stress, as shown by a decrease in malondialdehyde level and an increase in superoxide dismutase and catalase activities and glutathione level, was observed in the 30 mM-NAC-treated group in comparison to cells treated with H2O2 alone.

CONCLUSION:

This study demonstrates the potential benefits of pharmacological preconditioning of diabetic-mouse-derived MSCs with NAC for amelioration of apoptosis and oxidative stress in H2O2 induced injury.

KEYWORDS:

N-acetyl cysteine; apoptosis; caspase-3; nuclear factor-κB; survival

PMID:
26923123
DOI:
10.1016/j.jcma.2015.09.005
[Indexed for MEDLINE]
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