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Effects of metformin on lipopolysaccharide induced inflammation by activating fibroblast growth factor 21
Ezgi Kar1, Özkan Alataş2, Varol Şahıntürk3
1Department of Medical Biochemistry, Çanakkale Onsekiz Mart University, Çanakkale, Turkey.
Abstract:
Lipopolysaccharide (LPS) is a component of the cell wall of Gram-negative bacteria that produces endotoxemia, which may cause septic shock. Metformin (MET) is a widely used hypoglycemic drug that exhibits anti-inflammatory properties. Fibroblast growth factor 21 (FGF21) is an endocrine polypeptide that affects glucose and lipid metabolism, and also possesses anti-inflammatory properties. We investigated the effects of MET and FGF21 on inflammation due to LPS induced endotoxemia in male rats. Animals were divided into five groups: control, LPS, pre-MET LPS, LPS + 1 h MET and LPS + 3 h MET. Serum levels of alanine aminotransferase, aspartate aminotransferase, FGF2, interleukin-10 and tumor necrosis factor alpha were measured. Malondialdehyde, myeloperoxidase and FGF21 levels were measured in liver tissue samples. Histopathology of all groups was assessed using hematoxylin and eosin stained sections. LPS caused severe inflammatory liver damage. MET exhibited a partially protective effect and reduced inflammation significantly. FGF21 is produced in the liver following inflammation and MET may increase its production.
Insights
Metformin (MET) partially protected male rats against liver inflammation caused by lipopolysaccharide (LPS) induced endotoxemia. MET may enhance the production of anti-inflammatory Fibroblast Growth Factor 21 (FGF21).
Area of Science:
- Biochemistry
- Pharmacology
- Pathology
Background:
- Lipopolysaccharide (LPS) from Gram-negative bacteria causes endotoxemia and potentially septic shock.
- Metformin (MET), a hypoglycemic drug, has demonstrated anti-inflammatory effects.
- Fibroblast Growth Factor 21 (FGF21) is an endocrine polypeptide involved in metabolic regulation and inflammation.
Purpose of the Study:
- To investigate the protective effects of Metformin (MET) and Fibroblast Growth Factor 21 (FGF21) against lipopolysaccharide (LPS)-induced endotoxemia in male rats.
- To assess the impact of MET on liver inflammation markers and FGF21 production.
Main Methods:
- Male rats were divided into control, LPS-induced endotoxemia, and various MET treatment groups (pre-treatment, 1-hour post-treatment, 3-hour post-treatment).
- Serum levels of liver enzymes (ALT, AST), cytokines (IL-10, TNF-α), and FGF2 were measured.
- Liver tissue analysis included malondialdehyde, myeloperoxidase, FGF21 levels, and histopathology (H&E staining).
Main Results:
- LPS administration resulted in significant inflammatory liver damage.
- Metformin (MET) treatment demonstrated a partial protective effect, significantly reducing inflammation.
- FGF21 levels increased in the liver following inflammation, and MET appeared to enhance its production.
Conclusions:
- Metformin (MET) offers partial protection against LPS-induced endotoxemia and associated liver inflammation in male rats.
- The anti-inflammatory effects of MET may be partly mediated by an increase in hepatic Fibroblast Growth Factor 21 (FGF21) production.
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