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

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.