Objective
In this study, zebrafish was used as a biological model to induce type 2 diabetes mellitus through glucose. Then, the effect of metformin and silibinin combination was examined on elevated blood glucose, intestinal tissues, liver enzymes, and TNF-α, IFN-γ, INL1β genes as inflammation marker genes.
Methods
The liver enzymes (AST, ALT, and ALP) derived from fish viscera homogenate supernatants were assayed in an auto-analyzer. The expression of target genes was quantified on RNA extracted from the tails by an in-house RT-PCR method, with fine intestine tissue staining performed by hematoxylin and eosin protocol (H&E).
Result
In the glucose-free treatments, metformin and silymarin decreased the levels of AST, ALT, and ALP enzymes in the blood. The combination of these two drugs had also a significant role in reducing glucose levels. The body weight increased significantly in the control group which was affected by glucose concentration, with the lowest body weight gain observed in the metformin group. The expression of INL-1β gene was significantly enhanced in the control group and the highest IFN-γ expression was observed in both control groups with glucose (G + CTRL) and without glucose (G-CTRL) (p < 0.05). The lowest level of TNF-α gene expression was observed in the control + glucose group (G + CTRL) (p < 0.05). Diabetic state causes weak absorption whereby the fish body demands to increase absorption level by enhancing the amount of acidic goblet cells thereby acidifying the environment in the gastric tracts.
Conclusion
Collectively, this study indicated that treatment with metformin and Silibinin could improve metabolic-mediated performances by reducing the expression of inflammatory genes and blood glucose, modulating liver enzymes, and ameliorating the intestinal inflammation in type 2 diabetic zebrafish model.
The interferon (IFN) proteins, including IFN-alpha2b have been used as antifibrogenic factors to modulate the expression of extracellular matrix (ECM) proteins associated with fibroproliferative disorders in skin. This study was conducted to determine if IFN-alpha2b can counteract the fibrogenic effects of insulin-like growth factor-1 (IGF-1), which is present in large quantity in fibrotic dermis. Human dermal fibroblasts were established in culture and treated with either vehicle (control), 2000 U/ml IFN-alpha2b alone, 100 ng/ml IGF-1 alone, or both IFN-alpha2b and IGF-1. The results showed that treatment with IFN-alpha2b inhibited the proliferation of dermal fibroblasts, reduced the steady-state levels of type I procollagen mRNA in the cells, and reduced the production of collagen as measured by hydroxyproline in conditioned medium. However, this treatment also increased levels of collagenase mRNA in the cells and collagenase activity in the medium. Cells treated with IGF-1 showed increased proliferation and collagen production and decreased collagenase. Cells treated with both IFN-alpha2b and IGF-1 exhibited a 44% reduction in hydroxyproline production (p < 0.05) and a 363% increase in collagenase activity over cells treated with IGF-1 alone (p < 0.01). These results indicate that when IGF-1 and IFN-alpha2b are used individually, they function as fibrogenic and antifibrogenic factors for dermal fibroblasts, respectively, and that fibrogenic effects of IGF-1 on cell proliferation, collagen, and collagenase expression can be counteracted by IFN-alpha2b. These findings support the potential use of IFN-alpha2b as a therapeutic agent for treatment of fibroproliferative disorders, such as postburn hypertrophic scarring.
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