Chronic pancreatitis: role of oxidative stress and antioxidants

• Published in: Free radical research Vol. 47; no. 11; p. 941
• Main Authors: Bhardwaj, P, Yadav, R K
• Format: Journal Article
• Language: English
• Published: England 01-11-2013
• Subjects: Animals; Antioxidants - metabolism; Free Radicals - metabolism; Humans; Oxidative Stress - physiology; Pancreatitis, Chronic - metabolism; Reactive Oxygen Species - metabolism
• ISSN: 1029-2470
• DOI: 10.3109/10715762.2013.804624

Chronic pancreatitis (CP) is characterized by pain, and exocrine and endocrine insufficiency of pancreas. Several hypotheses have been put forward to explain the hitherto partially understood pathophysiology of CP. In the past decade, animal and clinical studies have suggested that an increased chronic oxidative stress (OS) plays a key role in pathophysiology of CP and perpetuates its clinical and histological symptoms (pain and fibrosis-necrosis, respectively). Mounting OS in pancreatic acinar cells is a result of overproduction of free radicals (FR) during xenobiotic metabolism. It has been shown that Phase I cytochrome P450 enzymes of xenobiotic pathway are induced when exposed to a xenobiotic overload including alcohol, tobacco, smoke and other dietary toxins, which exceeds the capacity of Phase II conjugation due to limited glutathione availability. Consequently, there is an overload of toxic metabolites as well as FR. Additionally, bioactivation of subsequently entering compounds may occur increasing their toxicity. Such an imbalance overwhelms the antioxidant capacity of the body resulting in undefended chronic OS that derails the normal physiology of pancreatic acinar cells since FR act as second messengers controlling the cellular signaling. OS hypothesis is further supported by the studies that demonstrated that antioxidant supplementation ameliorated pain. Moreover, animal studies have demonstrated a cessation of fibrotic cascade with antioxidant supplementation. In a recent large randomized controlled trial, it was demonstrated that antioxidant supplementation led to a significant reduction in pain, and also lowered the OS in patients with alcoholic or idiopathic CP.