Melatonin protects from hepatic reperfusion injury through inhibition of IKK and JNK pathways and modification of cell proliferation

• Published in: Journal of pineal research 2009-01, Vol.46 (1), p.8-14
• Main Authors: Liang, Rui, Nickkholgh, Arash, Hoffmann, Katrin, Kern, Michael, Schneider, Heinz, Sobirey, Michael, Zorn, Markus, Büchler, Markus W., Schemmer, Peter
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Biological and medical sciences; c-Jun N-terminal kinase; Cardiology. Vascular system; Cell Proliferation - drug effects; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; I-kappa B Kinase - antagonists & inhibitors; I-kappa B Kinase - metabolism; IKK; Immunohistochemistry; ischemia/reperfusion injury; JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors; JNK Mitogen-Activated Protein Kinases - metabolism; Liver - blood supply; Liver - enzymology; Liver - pathology; Medical sciences; melatonin; Melatonin - pharmacology; Nitric Oxide Synthase Type II - metabolism; nuclear factor κB; Oxidative Stress - drug effects; proliferation; Rats; Rats, Sprague-Dawley; Reperfusion Injury - drug therapy; Reperfusion Injury - enzymology; Reperfusion Injury - prevention & control; Signal Transduction - drug effects; Vertebrates: endocrinology
• ISSN: 0742-3098; 1600-079X
• DOI: 10.1111/j.1600-079X.2008.00596.x

:  Reactive oxygen species (ROS) are involved in pathophysiology of ischemia/reperfusion injury. Melatonin is a potent scavenger of ROS. Thus, this study was designed to elucidate its effects in a combined hepatic warm ischemia and resection model. The right lateral and caudate lobes (32% of liver volume) of Sprague–Dawley rats underwent warm ischemia for 30 min followed by reperfusion and subsequent resection of the nonischemic liver tissue. Some rats were gavaged with 50 mg/kg melatonin 2 hr before the onset of experiments. Controls received the same volume of microcrystalline cellulose. Survival, transaminases, histology, flow cytometry, inducible nitric oxide synthase (iNOS) expression, and activation of signal transduction pathways [c‐Jun N‐terminal kinase (JNK), cJUN, IκB kinase α (IKKα), proliferating cell nuclear antigen (PCNA), and Ki67] were assessed for hepatic injury, oxidative stress, and cell proliferation. Melatonin significantly improved animal survival and decreased transaminase levels, the indices for necrosis, liver damage, leukocyte infiltration, and iNOS expression. In parallel, the expression of IKKα, JNK1, and cJUN decreased by 35–50% after melatonin (P