Concurrent metformin and silibinin therapy in diabetes: assessments in zebrafish ( Danio rerio ) animal model
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RESEARCH ARTICLE
Concurrent metformin and silibinin therapy in diabetes: assessments in zebrafish (Danio rerio) animal model Hassan Mohammadi 1 & Hamed Manouchehri 1 Mohammad Reza Khorramizadeh 3
&
Reza Changizi 1 & Fatemeh Bootorabi 2 &
Received: 1 July 2020 / Accepted: 14 September 2020 # The Author(s) 2020
Abstract 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 autoanalyzer. 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. Keywords Zebrafish . Type 2 diabetes . Metformin . Silibinin
Introduction Type 2 diabetes, obesity, and cardiovascular problems, linked to unhealthy life styles and metabolic-driven disorders, have * Hamed Manouchehri [email protected] Hassan Mohammadi [email protected] Reza Changizi [email protected] Fatemeh Bootorabi [email protected] Mohammad Reza Khorramizadeh [email protected]
grown dramatically for decades globally [1, 2]. Nowadays, the disease associated with obesity and high blood glucose are becoming a leading cause of death. Metformin is one of the popular medicines for patients with type 2 diabetes. 1
Department of Aquaculture Science, Babol Branch, Islamic Azad University, Babol, Iran
2
Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
3
Biosensor Research Center, Endocrinology and Metabolism Molecular-Ce
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