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

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• 作者：Fatima Ali^a ; ^b ; ^{Fatemei.ali@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Mohsin Khan^b ; ^c ; Shaheen N. Khan^b ; Sheikh Riazuddin^a ; ^b ; ^d
• 关键词：apoptosis ; caspase-3 ; N-acetyl cysteine ; nuclear factor-κB ; survival
• 刊名：Journal of the Chinese Medical Association
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：79
• 期：3
• 页码：122-129
• 全文大小：1555 K

文摘

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 30mM NAC for 1 hour followed by oxidative injury with 100μM 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 30mM-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 30mM-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.