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Preparing a Mice Model of Severe Acute Pancreatitis via a Combination of Caerulein and Lipopolysaccharide Intraperitoneal Injection
Published on: May 10, 2024
Dimethyl fumarate ameliorates acute pancreatitis in rodent
Lourdes Robles1, Nosratola D Vaziri, Shiri Li
1From the Departments of *Surgery and †Medicine, University of California, Irvine, CA.
Objectives:
Pancreatitis is a complex inflammatory disorder, ranging from a mild attack, to severe and potentially fatal condition. Dimethyl fumarate (DMF), a potent antioxidant and anti-inflammatory, has been used medicinally for decades. The purpose of this study was to test the hypothesis that treatment with DMF may ameliorate acute pancreatitis (AP) in a rodent model.
Methods:
Rats were treated with DMF (25 mg/kg) 24 hours prior to AP induction with l-arginine (3 g/kg). At 72 hours, the pancreas was processed for histology. Serum amylase, lactate dehydrogenase, pancreatic trypsin, and lipid peroxidation product (malondialdehyde) were evaluated. Key cytokines and chemokines in the supernatant of lipopolysaccharide-stimulated splenocytes were also determined.
Results:
Pancreata from DMF-treated rats showed reductions in the severity of inflammatory cell infiltration, acinar damage, perilobar edema, and cell necrosis. This was associated with significantly lower amylase and malondialdehyde but not lactate dehydrogenase or trypsin levels. The apoptotic pancreatic cells (cleaved caspase 3 positive) were significantly lower in the DMF-treated rats. Lipopolysaccharide-stimulated splenocytes treated with DMF produced a significantly lower amount of key inflammatory mediators.
Conclusion:
Administration of DMF attenuates AP in rats.
Insights
Dimethyl fumarate (DMF) treatment reduced inflammation and cell damage in a rat model of acute pancreatitis (AP). This suggests DMF may be a potential therapeutic agent for managing AP.
Area of Science:
- Gastroenterology
- Immunology
- Pharmacology
Background:
- Acute pancreatitis (AP) is a serious inflammatory condition with variable severity.
- Dimethyl fumarate (DMF) is recognized for its antioxidant and anti-inflammatory properties.
Purpose of the Study:
- To investigate the potential of Dimethyl fumarate (DMF) in mitigating acute pancreatitis (AP) in a rodent model.
- To test the hypothesis that DMF treatment can ameliorate AP.
Main Methods:
- Rats received DMF 24 hours before AP induction via l-arginine.
- Histological analysis of pancreatic tissue was performed 72 hours post-induction.
- Biochemical markers (amylase, LDH, trypsin, malondialdehyde) and cytokine/chemokine levels from stimulated splenocytes were assessed.
Main Results:
- DMF treatment significantly reduced pancreatic inflammation, acinar damage, edema, and necrosis.
- Lower levels of serum amylase and malondialdehyde were observed in DMF-treated rats.
- DMF administration decreased apoptotic pancreatic cells and inflammatory mediator production by splenocytes.
Conclusions:
- Dimethyl fumarate (DMF) demonstrates a protective effect against acute pancreatitis (AP) in a rat model.
- DMF attenuates key inflammatory and apoptotic pathways involved in AP pathogenesis.
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