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World J Gastroenterol. Dec 28, 2010; 16(48): 6087-6097
Published online Dec 28, 2010. doi: 10.3748/wjg.v16.i48.6087
Hepatoprotective actions of melatonin: Possible mediation by melatonin receptors
Alexander M Mathes
Alexander M Mathes, Department of Anesthesiology, Critical Care and Pain Medicine, Saarland University Hospital, Kirrberger Straße, D-66421 Homburg (Saar), Germany
Author contributions: Mathes AM made all the contributions of this paper.
Supported by (in part) Grants from the European Society of Anesthesiology and the HOMFOR Homburger Forschungsförderung
Correspondence to: Alexander M Mathes, MD, Department of Anesthesiology, Critical Care and Pain Medicine, Saarland University Hospital, Kirrberger Straße, D-66421 Homburg (Saar), Germany. alexander.mathes@uks.eu
Telephone: +49-6841-1662271 Fax: +49-6841-1622833
Received: June 28, 2010
Revised: August 8, 2010
Accepted: August 15, 2010
Published online: December 28, 2010
Abstract

Melatonin, the hormone of darkness and messenger of the photoperiod, is also well known to exhibit strong direct and indirect antioxidant properties. Melatonin has previously been demonstrated to be a powerful organ protective substance in numerous models of injury; these beneficial effects have been attributed to the hormone’s intense radical scavenging capacity. The present report reviews the hepatoprotective potential of the pineal hormone in various models of oxidative stress in vivo, and summarizes the extensive literature showing that melatonin may be a suitable experimental substance to reduce liver damage after sepsis, hemorrhagic shock, ischemia/reperfusion, and in numerous models of toxic liver injury. Melatonin’s influence on hepatic antioxidant enzymes and other potentially relevant pathways, such as nitric oxide signaling, hepatic cytokine and heat shock protein expression, are evaluated. Based on recent literature demonstrating the functional relevance of melatonin receptor activation for hepatic organ protection, this article finally suggests that melatonin receptors could mediate the hepatoprotective actions of melatonin therapy.

Keywords: Antioxidant enzymes; Hemorrhagic shock; Hepatoprotection; Ischemia; Liver; Liver function; Melatonin; Melatonin receptor; Ramelteon; Reperfusion; Sepsis; Toxic liver injury