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World J Gastrointest Pharmacol Ther. Feb 6, 2010; 1(1): 21-26
Published online Feb 6, 2010. doi: 10.4292/wjgpt.v1.i1.21
N-acetylcysteine in acute pancreatitis
Laura Ramudo, Manuel A Manso
Laura Ramudo, Manuel A Manso, Department of Physiology and Pharmacology, University of Salamanca, Salamanca 37007, Spain
Author contributions: Manso MA and Ramudo L wrote the paper.
Correspondence to: Manuel A Manso, PhD, Department of Physiology and Pharmacology, University of Salamanca, Salamanca 37007, Spain. mamanso@usal.es
Telephone: +34-923294673 Fax:+34-923294673
Received: December 23, 2009
Revised: January 13, 2010
Accepted: January 20, 2010
Published online: February 6, 2010
Abstract

Premature trypsinogen activation and production of oxygen free radicals (OFR) are early pathogenic events which occur within acinar cells and trigger acute pancreatitis (AP). OFR exert their harmful effects on various cell components causing lipid peroxidation, disturbances in calcium homeostasis and DNA damage, which lead to increased cell injury and eventually cell death. This review presents the most recent data concerning the effects of N-Acetylcysteine (NAC), in the treatment of AP. NAC is an antioxidant capable of restoring the levels of Glutathione, the most important cellular antioxidant. Studies show the beneficial effects of NAC treatment in preventing OFR production and therefore attenuating oxidative damage. Additionally, NAC treatment has been shown to prevent the increase in cytosolic Ca2+ concentration and reduce the accumulation of enzymes in acinar cells during AP. The prevention, by NAC, of these pathological events occurring within acinar would contribute to reducing the severity of AP. NAC is also capable of reducing the activation of transcription factors especially sensitive to the cellular redox state, such as Nuclear factor-κB, signal transducer and activator of transcription-3 and mitogen-activated protein kinase. This leads to a down-regulation of cytokines, adhesion molecules and chemokine expression in various cell types during AP. These findings point to NAC as a powerful therapeutic treatment, attenuating oxidative-stress-induced cell injury and other pathological events at early stages of AP, and potentially contributing to reducion in the severity of disease.

Keywords: Acute pancreatitis; Calcium homeostasis; Cell cycle; Glutathione; Monocyte chemoattractant protein-1; N-acetylcysteine; Oxygen free radicals; Transcription factors