Role of free radicals in pancreatitis

Shin Hamada, Tooru Shimosegawa

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Acute pancreatitis and chronic pancreatitis show distinct clinical features, but they share common pathological changes in the pancreas. The establishment of inflammation within the pancreas involves a multiple process, and free radicals play crucial roles during the exacerbation of inflammation. Reactive oxygen species and reactive nitrogen species are produced by acinar cells, pancreatic stellate cells and infiltrating inflammatory cells. These molecules further activate downstream signaling pathway. In the case of acute pancreatitis, acinar cell damage leads to free radical production, which triggers cytokine production. Infiltrating neutrophils further create free radicals by 'respiratory burst', resulting in amplification of tissue damage. Excessive free radicals also contribute to multiple organ failure. In case of chronic pancreatitis, free radicals help to establish the persistent inflammation referred to as 'necrosis-fibrosis sequences'. Pancreatic stellate cells are activated by free radicals, leading to the increased production of cytokines and extracellular matrix, finally developing irreversible fibrosis in the pancreas. Free radicals exert these effects not only by direct injury to the cellular components, but also by activating multiple signaling pathways, such as NF-κB or mitogen-activated protein kinase. Inhibition of free radicals by free radical scavengers or inhibitors of reactive oxygen species-generating enzyme shows therapeutic effects in the experimental model, and clinical application is also expected. Targeting the free radical-generating system would be a novel therapeutic strategy against acute and chronic pancreatitis.

Original languageEnglish
Title of host publicationFree Radical Biology in Digestive Diseases
EditorsYuji Naito, Toshikazu Yoshikawa, Makoto Suematsu
Pages156-163
Number of pages8
DOIs
Publication statusPublished - 2010 Dec

Publication series

NameFrontiers of Gastrointestinal Research
Volume29
ISSN (Print)0302-0665

ASJC Scopus subject areas

  • Gastroenterology

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