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Sodium Taurocholate Induced Severe Acute Pancreatitis in C57BL/6 Mice
Published on: June 28, 2021
Platelet activating factor antagonism reduces the systemic inflammatory response in a murine model of acute
1Department of Surgery, UCLA Medical Center, Los Angeles, CA 90095, USA.
Background:
The platelet activating factor (PAF) antagonist, Lexipafant, has been used in experimental models and clinical trials to treat severe acute pancreatitis (AP). The purpose of this study was to determine whether Lexipafant reduces the local and systemic components of AP in a murine model of mild, edematous AP.
Materials And Methods:
Forty-eight female Swiss-Webster mice were divided into four groups. Group 1 received 50 microl of saline ip every hour for 6 h (sham). Group 2 received saline treatment, plus Lexipafant (25 mg/kg dose ip, every 3 h starting 1 h after the first saline injection) (sham/Lex). Group 3 received cerulein (50 microg/kg dose ip, every hour for 6 h) (AP). Group 4 received AP, plus therapeutic treatment with Lexipafant (AP/Lex). Animals were sacrificed 3 h after the last injection. Serum cytokine levels were determined by ELISA. Standard assays were performed for serum amylase activity and lung myeloperoxidase activity (MPO). Histology was scored by two blinded investigators.
Results:
Serum cytokines (TNFalpha, IL-1beta), lung MPO, and serum amylase activity were reduced by PAF antagonism. Histology showed a trend toward improvement with Lexipafant, but did not reach statistical significance.
Conclusion:
The PAF antagonism reduces the severity of systemic inflammation when given after the induction of mild AP in mice. These results suggest that Lexipafant may be useful in the treatment of mild pancreatitis after its clinical onset.
Insights
Platelet activating factor (PAF) antagonism with Lexipafant reduced systemic inflammation in a mouse model of mild acute pancreatitis (AP). This suggests Lexipafant may treat mild AP after symptom onset.
Area of Science:
- Gastroenterology
- Inflammation research
- Pharmacology
Background:
- Platelet activating factor (PAF) antagonists, like Lexipafant, have been explored for treating severe acute pancreatitis (AP).
- Investigating Lexipafant's efficacy in a murine model of mild, edematous AP is crucial for understanding its therapeutic potential.
Purpose of the Study:
- To evaluate the effect of Lexipafant on local and systemic inflammatory markers in mild AP.
- To determine if therapeutic administration of Lexipafant can mitigate the severity of acute pancreatitis.
Main Methods:
- A murine model of mild acute pancreatitis was induced using cerulein.
- Mice received either saline or Lexipafant treatment post-induction.
- Serum cytokine levels, amylase activity, and lung myeloperoxidase (MPO) activity were measured.
Main Results:
- PAF antagonism significantly reduced serum cytokines (TNF-alpha, IL-1beta), serum amylase, and lung MPO activity.
- Histological analysis indicated a non-significant trend towards improvement with Lexipafant treatment.
Conclusions:
- Therapeutic administration of Lexipafant effectively reduces systemic inflammation in mild acute pancreatitis in mice.
- These findings support the potential utility of Lexipafant for treating mild pancreatitis following clinical manifestation.
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