title: N-Acetyl cysteine protects diabetic mouse derived mesenchymal stem cells from hydrogen-peroxide-induced injury: A novel hypothesis for autologous stem cell transplantation.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Fatima
authors.initials: F
authors.lastname: Ali
authors.affiliation: 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.
authors.forename: Mohsin
authors.initials: M
authors.lastname: Khan
authors.affiliation: National Center of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: Shaheen N
authors.initials: SN
authors.lastname: Khan
authors.affiliation: 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.
authors.forename: Sheikh
authors.initials: S
authors.lastname: Riazuddin
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000633:toxicity*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D013311:Streptozocin; D014182:Transplantation, Autologous
chemical_list: D000975:Antioxidants; D013311:Streptozocin; D006861:Hydrogen Peroxide; D000111:Acetylcysteine
keywords: N-acetyl cysteine; apoptosis; caspase-3; nuclear factor-κB; survival