ABSTRACT
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.
ABSTRACT
This study aims to investigate the effect of hydroethanolic extracts of Cynara scolymus (C. scolymus) leaf (CLHE) and C. scolymus flower (CFHE) on the hepatic histopathological lesions and functional biochemical changes induced by type 2 diabetes mellitus (T2DM). The rat model of T2DM was induced by intraperitoneal injection of streptozotocin (STZ) in a dose of 60 mg/kg for 15 minutes following nicotinamide (NA) (60 mg/kg). The rats were allocated into four groups: group 1 (negative control), group 2 (diabetic control), group 3 (diabetic rats supplemented with 100 mg/kg/day CLHE), and group 4 (diabetic rats supplemented with 100 mg/kg/day CFHE). Treatment with CLHE and CFHE, for the study duration of 28 days, significantly improved the deteriorated hepatic glycogen content, glycogen phosphorylase, glucose-6-phosphatase activities, serum fructosamine levels, lipid profile, aspartate transaminase activities, and alanine transaminase activities as well as serum insulin and C-peptide levels. The elevated liver lipid peroxidation and the decreased activities of superoxide dismutase and glutathione peroxidase were significantly alleviated. The elevated expression of the proinflammatory cytokine tumor necrosis factor-α in the liver of diabetic rats was significantly reduced by treatments with CLHE and CFHE. NA/STZ-induced T2DM exhibited hepatic histopathological changes in the form of disordered hepatocytes, cytoplasm dissolution, and mononuclear leukocytic infiltration. The electron microscopic ultrastructure study revealed damaged mitochondria with ill-defined cristae and fragmentation of the rough endoplasmic reticulum. Treatments with CLHE and CFHE remarkably amended these histopathological and EM ultrastructural changes. In conclusion, both CLHE and CFHE may have antidiabetic and improvement effects on the liver function and structural integrity, which may be mediated, at least in part, via suppression of inflammation and oxidative stress and enhancement of the antioxidant defence system.
