The Protective Effect of Melatonin Against Induced Oxidative Stress on Adipose-Derived Stem Cells (ASCS)

Background and Aim: Adipose-derived stem cells (ASCs) are oneof the cellular populations in adipose tissue with a high potency ofdifferentiation to specific lineages. These stem cells, based on theirtherapeutic potential to repair and regenerate damaged tissue, haveapplications in regenerative medicine. Melatonin is a natural compoundthat secret by the pineal gland and several studies investigated that it hasstrong antioxidant effect against free radicals. In this study, we aimed todetermine the cytoprotective effects of melatonin on ASCs that inducedby H2O2.Methods: We isolate human adipose-derived stem cells (hASCs) fromadipose tissue. Then we cultured them with different dosages of hydrogenperoxide and melatonin for a period of 3 hours. MTT assay was usedto assess the IC50 of melatonin and H2O2. We also measured the H2O2 -induced cytotoxicity in cultured ASCs with LDH assay. Apoptosis analysiswas investigated by using the flowcytometric annexin V/propidium iodide(PI) assay. The intracellular level of produced reactive oxygen species(ROS) during exposure to melatonin and H2O2 was assessed based onthe oxidation of fluorescent probe 2 7 -dichlorofluorescein (DCFH).Furthermore, the signaling pathway of Nrf2/ HO-1 in ASCs treated withmelatonin and H2O2 was studied.Results: Hydrogen peroxide treatment caused an incremental increasein cell death. Melatonin lonely had no damaging effects on ASCs inH2O2-free condition. ASCs co-treated with melatonin in the presence ofhydrogen peroxide prevented ASCs from cell death in a dose-dependentmanner. Co-treatment of ASCs with melatonin showed significantly fewerapoptotic cells. The release of LDH was considerably induced by H2O2,while melatonin pretreatment dose-dependently suppressed LDH releasein ASCs. The result of this study suggests that melatonin protects the ASCsagainst oxidative stress induced by H2O2. It is proposed that melatonininvolves in the control of Nrf2 in ASCs.Conclusion: In conclusion, melatonin seems to be an endogenousantioxidant agent with proficient free radical scavenging activity and mayact as an effective adjunct in fat grafting in tissues.

کلیدواژه ها:

Melatonin ، Oxidative stress ، Adipose ، Derived Stem Cells (ASCs)