Research Paper Volume 10, Issue 10 pp 2954—2972

Melatonin prevents senescence of canine adipose-derived mesenchymal stem cells through activating NRF2 and inhibiting ER stress

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Figure 6. Melatonin pretreatment increases the survival rate and curative effect of cADMSCs transplantation. (A) Food intake, (B) water intake, and (C) liver index of experimental dogs. (D-F) Effect of CCl4 injection and cADMSCs transplantation on blood AST (D), ALT (E) and ALB (F). (G) Frozen liver sections obtained 5 days after cADMSCs transplantation. Bar = 200 μm (H) HE staining of liver sections from CCl4-injected dogs 5 days after cADMSCs transplantation. Bar = 50 μm. (I) Histopathological scores of HE-stained canine liver sections. (J) Effects of CCl4 injection and cADMSCs transplantation on the levels of ERS-related transcripts in canine liver. (K) Proposed model of melatonin inhibition of ERS. According to this model, melatonin binding to MT1/MT2 receptor results in activation of NRF2 which then activates ERAD and inhibits NF-κB signaling, overall resulting in inhibition of ERS. A dotted line indicates information obtained from other studies.