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DPP4 Inhibitor Attenuates Severe Acute Pancreatitis-Associated Intestinal Inflammation via Nrf2 Signaling

Xiang Zhou1, Weiming Wang1, Cheng Wang2

  • 1Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, China.

Oxidative Medicine and Cellular Longevity
|December 13, 2019
PubMed

Insights

Sitagliptin, a DPP4 inhibitor, protects against severe acute pancreatitis (SAP) and associated intestinal injury by reducing oxidative stress and inflammation. This protection involves the Nrf2-NF-κB pathway, highlighting a potential therapeutic target for SAP.

Area of Science:

  • Gastroenterology
  • Pharmacology
  • Molecular Biology

Background:

  • Severe acute pancreatitis (SAP) is a critical condition with high mortality, frequently leading to multiple organ dysfunction syndrome (MODS).
  • Intestinal injury is a significant factor in MODS development and disease progression during SAP.

Purpose of the Study:

  • To investigate the protective effects of the DPP4 inhibitor sitagliptin on intestinal injury in severe acute pancreatitis (SAP).
  • To elucidate the molecular mechanisms underlying sitagliptin's protective action, focusing on oxidative stress, inflammation, and the Nrf2-NF-κB pathway.

Main Methods:

  • In vitro and in vivo models of SAP were utilized.
  • Sitagliptin treatment was administered to SAP mouse models.
  • Expression levels of Nrf2 and NF-κB were analyzed.
  • Experiments were conducted using Nrf2 knockout (Nrf2-/-) mice to assess the role of Nrf2.

Main Results:

  • Sitagliptin demonstrated significant protection against SAP-induced intestinal injury in both in vitro and in vivo settings.
  • Sitagliptin treatment suppressed oxidative stress and inflammatory responses in SAP models.
  • In sitagliptin-treated mice, Nrf2 expression was upregulated, while NF-κB expression was downregulated.
  • Nrf2-/- mice exhibited exacerbated pancreatic and intestinal injury compared to wild-type mice, indicating Nrf2's crucial role.

Conclusions:

  • Sitagliptin offers a protective effect against severe acute pancreatitis-associated intestinal injury.
  • The mechanism involves the inhibition of reactive oxygen species (ROS) possibly through the inactivation of the Nrf2-NF-κB pathway.
  • Sitagliptin represents a potential therapeutic agent for mitigating intestinal damage in SAP.

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