2',4',6'-Tris(methoxymethoxy) chalcone (TMMC) attenuates the severity of cerulein-induced acute pancreatitis and associated lung injury.

Abstract

Acute pancreatitis (AP) is an inflammatory disease involving acinar cell injury and rapid production and release of inflammatory cytokines, which play a dominant role in local pancreatic inflammation and systemic complications. 2',4',6'-Tris (methoxymethoxy) chalcone (TMMC), a synthetic chalcone derivative, displays potent anti-inflammatory effects. Therefore, we aimed to investigate whether TMMC might affect the severity of AP and pancreatitis-associated lung injury in mice. We used the cerulein hyperstimulation model of AP. Severity of pancreatitis was determined in cerulein-injected mice by histological analysis and neutrophil sequestration. The pretreatment of mice with TMMC reduced the severity of AP and pancreatitis-associated lung injury and inhibited several biochemical parameters (activity of amylase, lipase, trypsin, trypsinogen, and myeloperoxidase and production of proinflammatory cytokines). In addition, TMMC inhibited pancreatic acinar cell death and production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 by inhibiting NF-κB and extracellular signal-regulated protein kinase 1/2 (ERK1/2) activation. Neutralizing antibodies for TNF-α, IL-1β, and IL-6 inhibited cerulein-induced cell death in isolated pancreatic acinar cells. Moreover, pharmacological blockade of NF-κB/ERK1/2 reduced acinar cell death and production of TNF-α, IL-1β, and IL-6 in isolated pancreatic acinar cells. In addition, posttreatment of mice with TMMC showed reduced severity of AP and lung injury. Our results suggest that TMMC may reduce the complications associated with pancreatitis.

• Authors: Tae-Hyeon Kim, Gi-Sang Bae, Hyo-Jeong Oh, Min-Sun Kim, Kyoung-Chel Park, Bon Soon Koo, Byung-Jin Kim, Yun-Sik Yang, Dong-Eun Park, Jae-Hoon Lee, Sang-Wan Seo, Yong Kook Shin, Ki-Jung Yun, Dong Hwan Sohn, Hyung-Jin Kim, Hong-Seob So, Rae-Kil Park, Ho-Joon Song, Sung-Joo Park
• Journal: American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 301 Issue 4 Pg. G694-706 (Oct 2011) ISSN: 1522-1547 [Electronic] United States
• PMID: 21778460 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2',4',6'-tris(methoxymethoxy) chalcone
• Anti-Inflammatory Agents
• Chalcones
• Interleukin-1beta
• Interleukin-6
• NF-kappa B
• Tumor Necrosis Factor-alpha
• Ceruletide
• Peroxidase
• Mitogen-Activated Protein Kinases
• Lipase
• Amylases

Topics

• Amylases (blood)
• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Ceruletide
• Chalcones (therapeutic use)
• Interleukin-1beta (blood)
• Interleukin-6 (blood)
• Lipase (blood)
• Lung Injury (prevention & control)
• Mice
• Mice, Inbred C57BL
• Mitogen-Activated Protein Kinases (metabolism)
• NF-kappa B (metabolism)
• Pancreatitis (chemically induced, complications, drug therapy, pathology)
• Peroxidase (metabolism)
• Tumor Necrosis Factor-alpha (blood)