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Oxidative Medicine and Cellular Longevity
Volume 2015, Article ID 607271, 11 pages
Research Article

A Novel Antioxidant Multitarget Iron Chelator M30 Protects Hepatocytes against Ethanol-Induced Injury

1National Key Disciplines for Infectious Diseases, Shenzhen Third People’s Hospital, Shenzhen 518112, China
2Department of Immunobiology, Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou 510632, China
3Department of Anatomy, The University of Hong Kong, Pokfulam, Hong Kong
4Eve Topf Centers of Excellence, Technion, Rappaport Family Faculty of Medicine and Department of Pharmacology, 31096 Haifa, Israel

Received 13 October 2014; Accepted 14 January 2015

Academic Editor: Vittorio Calabrese

Copyright © 2015 Jia Xiao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The multitarget iron chelator, M30, is a novel antioxidant and protective agent against oxidative stress in a spectrum of diseases. However, there is no report regarding its role in liver diseases. Since oxidative stress is one of the major pathological events during the progression of alcoholic liver diseases, the protective effects and mechanisms of M30 on ethanol-induced hepatocyte injury were investigated in this study. Rat hepatocyte line BRL-3A was pretreated with M30 prior to ethanol treatment. Cell death, apoptosis, oxidative stress, and inflammation were examined. Specific antagonists and agonists were applied to determine the involvements of hypoxia inducible factor-1 alpha (HIF-1α) and its upstream adenylate cyclase (AC)/cyclic AMP (cAMP)/protein kinase A (PKA)/HIF-1α/NOD-like receptor 3 (NLRP3) inflammasome pathway. We found that M30 significantly attenuated ethanol-induced cellular death, apoptosis, production of reactive oxygen species (ROS), and secretion of inflammatory cytokines and inhibited activation of the AC/cAMP/PKA/HIF-1α/NLRP3 inflammasome pathway. Inhibition and activation of the AC/cAMP/PKA/HIF-1α pathway mimicked and abolished the effects of M30, respectively. In conclusion, inhibition of the AC/cAMP/PKA/HIF-1α/NLRP3 inflammasome pathway by M30 partially contributes to its attenuation of hepatocyte injury caused by ethanol exposure.