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World J Gastroenterol. Dec 14, 2014; 20(46): 17324-17329
Published online Dec 14, 2014. doi: 10.3748/wjg.v20.i46.17324
Oxidative stress and inflammatory signaling in cerulein pancreatitis
Ji Hoon Yu, Hyeyoung Kim
Ji Hoon Yu, New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 701-310, South Korea
Hyeyoung Kim, Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul 120-749, South Korea
Author contributions: All authors contributed to the manuscript.
Supported by National Research Foundation of Korea grant funded by the Korea government No. 2007-0056092
Correspondence to: Hyeyoung Kim, PhD, Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, South Korea.
Telephone: +82-2-21233125 Fax: +82-2-3645781
Received: June 6, 2014
Revised: July 26, 2014
Accepted: September 18, 2014
Published online: December 14, 2014

Oxidative stress is considered to be an important regulator of the pathogenesis of acute pancreatitis. Reactive oxygen species (ROS) regulate the activation of inflammatory cascades, the recruitment of inflammatory cells and tissue damage in acute pancreatitis. A hallmark of the inflammatory response in pancreatitis is the induction of cytokine expression, which is regulated by a number of signaling molecules including oxidant-sensitive transcription factors such as nuclear factor-κB (NF-κB) and activator protein-1 (AP-1), signal transducer and activator of transcription 3 (STAT3), and mitogen-activated protein kinases (MAPKs). Cross-talk between ROS and pro-inflammatory cytokines is mediated by NF-κB, AP-1, STAT3, and MAPKs; this crosstalk amplifies the inflammatory cascade in acute pancreatitis. Therapeutic studies have shown that antioxidants and natural compounds can have beneficial effects for patients with pancreatitis and can also influence the expression of proinflammatory cytokines in cerulein-induced pancreatitis. Since oxidative stress may activate inflammatory signaling pathways and contribute to the development of pancreatitis, antioxidant therapy may alleviate the symptoms or prevent the development of pancreatitis. Since chronic administration of high doses of antioxidants may have deleterious effects, dosage levels and duration of antioxidant treatment should be carefully determined.

Keywords: Reactive oxygen species, Inflammatory signaling, Cerulein pancreatitis

Core tip: The pathogenesis of acute pancreatitis is not completely elucidated. Oxidative stress may contribute to the development of acute pancreatitis. Evidence supporting the role of reactive oxygen species and cytokines as a risk for pancreatitis and the concept of antioxidant supplementation as a preventive approach for pancreatitis has been proposed. Here we review the literature on oxidative stress, cytokine expression, inflammatory signaling, and natural antioxidant supplementation using an experimental model of cerulein-induced acute pancreatitis.