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Reducing Pancreatic Fibrosis Using Antioxidant Therapy Targeting Nrf2 Antioxidant Pathway

A Possible Treatment for Chronic Pancreatitis

Kojayan, Greg Garo BS; Alizadeh, Reza Fazl MD; Li, Shiri MD, PhD; Ichii, Hirohito MD, PhD

doi: 10.1097/MPA.0000000000001433

Chronic pancreatitis is the progressive inflammation of the pancreas resulting in the irreversible damage of pancreatic structure and function by means of fibrosis. Chronic pancreatitis is most commonly caused by alcohol consumption, although the direct molecular etiology is unknown. Recent studies suggest oxidative stress as a catalyst for pancreatic stellate cell activation leading to the deposition of collagenous extracellular matrix causing pancreatic fibrosis. We review the effect of oxidative stress on pancreatic fibrogenesis and indicate the molecular pathways involved in preventing oxidant-related cell damage. Likewise, we summarize existing antioxidative therapies for chronic pancreatitis and discuss a novel nuclear factor erythroid 2–related factor 2 activator, dimethyl fumarate, and its potential to reduce fibrogenesis by downregulating pancreatic stellate cell activation.

From the Department of Surgery, University of California, Irvine, Orange, CA.

Received for publication February 2, 2019; accepted September 7, 2019.

Address correspondence to: Hirohito Ichii, MD, PhD, Department of Surgery, University of California Irvine, 333 City Blvd West, Suite 1205, Orange, CA 92868 (e-mail:

The authors declare no conflict of interest.

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.