RESUMO
OBJECTIVES: The aim of this study was to compare the effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) isolated from mice (xenogeneic) and rats (allogeneic) on liver injury induced by carbon tetrachloride (CCl4) as well as to explore the modulatory effects on of oxidative stress, apoptosis, inflammation, and Nrf2 expression. METHODS: Male Wistar rats were intraperitoneally injected with CCl4 (0.5 mL/kg) twice a week for 8 weeks. The animals were intravenously infused with BM-MSCs isolated from male mice or rats (1 × 106 cells/rat/week) into the lateral tail vein for 4 weeks. RESULTS: The treatment with BM-MSCs produced a significant increase in the diminished serum albumin level, a significant decrease in liver lipid peroxidation and an increase in glutathione content as well as SOD, GST, and GPx activities. Furthermore, BM-MSCs from both mice and rats produced a significant decrease in the elevated mRNA expression of liver CYP1A1, MMP-9, procollagen α1, TGF-ß1, and increase in expression of lowered IL-4, IL-10, cluster CD-105, and Oct3/4. In liver of CCl4-injected rats, the lower protein expression of Nrf2 was upregulated and higher expressions of caspase-3, TNF-R1, NF-κB p65, TNF-α, p53, and COX-2 were downregulated by mice and rats' BM-MSCs. Histologically, BM-MSCs from both mice and rats successfully improved liver structural integrity and protected against liver injury. CONCLUSIONS: The rats-derived BM-MSCs were significantly more potent than mice-derived BM-MSCs. Mice BM-MSCs and rats' BM-MSCs acted to improve CCl4-impaired liver function, structural integrity, fibrosis and cirrhosis in male Wistar rats via the suppression of oxidative stress, inflammation, and apoptosis and the enhancement of the antioxidant defense system.
RESUMO
The purpose of this study was to see how chrysin and/or bone marrow-derived mesenchymal stem cells (BM-MSCs) affected streptozotocin (STZ)/nicotinamide (NA)-induced diabetic rats as an animal model of type 2 diabetes mellitus (T2DM). Male Wistar rats were given a single intraperitoneal (i.p.) injection of 60 mg STZ/kg bodyweight (bw) 15 min after an i.p. injection of NA (120 mg/kg bw) to induce T2DM. The diabetic rats were given chrysin orally at a dose of 100 mg/kg bw every other day, BM-MSCs intravenously at a dose of 1 × 106 cells/rat/week, and their combination for 30 days after diabetes induction. The rats in the diabetic group displayed impaired oral glucose tolerance and a decrease in liver glycogen content and in serum insulin, C-peptide, and IL-13 levels. They also had significantly upregulated activities in terms of liver glucose-6-phosphatase and glycogen phosphorylase and elevated levels of serum free fatty acids, IL-1ß, and TNF-α. In addition, the diabetic rats exhibited a significant elevation in the adipose tissue resistin protein expression level and a significant decrease in the expression of adiponectin, insulin receptor-beta subunit, insulin receptor substrate-1, and insulin receptor substrate-2, which were associated with a decrease in the size of the pancreatic islets and in the number of ß-cells and insulin granules in the islets. The treatment of diabetic rats with chrysin and/or BM-MSCs significantly improved the previously deteriorated alterations, with chrysin combined with BM-MSCs being the most effective. Based on these findings, it can be concluded that combining chrysin with BM-MSCs produced greater additive therapeutic value than using them separately in NA/STZ-induced T2DM rats.
