Combination Treatments of 1-(N-Acetyl-6-Aminohexyl)-3-Hydroxy-2- Methylpyridin-4-One (CM1) With Deferiprone and Desferrioxamine Reduced Labile Iron Pool and Protected Oxidative Stress in Iron-Loaded Cultured HepatocytesKanokwan Kulprachakarn1, Kanjana Pangjit1,2, Chada Phisalaphong3, Suthat Fucharoen4, Robert C. Hider5 and Somdet Srichairatanakool1*
- *Corresponding Author:
- Somdet Srichairatanakool
Department of Biochemistry, Faculty of Medicine
Chiang Mai University, Chiang Mai 50200 Thailand
E-mail: [email protected]
Received Date: July 08, 2013; Accepted Date: July 10, 2013; Published Date: July 18, 2013
Citation: Kulprachakarn K, Pangjit K, Phisalaphong C, Fucharoen S, Hider RC, et al. (2013) Combination Treatments of 1-(N-Acetyl-6-Aminohexyl)-3-Hydroxy-2-Methylpyridin-4-One (CM1) With Deferiprone and Desferrioxamine Reduced Labile Iron Pool and Protected Oxidative Stress in Iron-Loaded Cultured Hepatocytes. Vitam Miner 2:115. doi: 10.4172/2376-1318.1000115
Copyright: © 2013 Kulprachakarn K, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Iron overload associated with oxidative stress is a serious problem in transfusion-dependent patients with β-thalassemia major. The increased iron overload in several organs may be caused by higher intestinal absorption along with less intensive chelation therapy. Liver iron overload could in turn facilitate the development or persistence of chronic progressive liver disease. Previous studies have shown that chelation with desferrioxamine (DFO) and deferiprone (DFP) substantially reduced body-iron scores in β-thalassemia patients with transfusional iron overload. We have synthesized and characterized a new bidentate iron chelator, 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2- methylpyridin-4-one (CM1). The compound can efficiently scavenge iron from both ferrous and ferric salts and plasma non-transferrin bound iron (NTBI). In this study we have studied the efficacy of the CM1 treatment on the decrease of levels of the labile iron pool (LIP) and reactive oxygen species (ROS) in iron-loaded mouse hepatocyte and HepG2 cell cultures. The isolated hepatocytes were treated with DFP, DFO and CM1 at different concentrations. The treated cells were analyzed for intracellular LIP using the calcein fluorescent technique and ROS levels using the dichlorofluorescein (DCF) fluorescent method. It was found that CM1 reduced the levels of intracellular LIP and hydrogen peroxideinduced ROS in both treated cells in a concentration-dependent manner. The combination treatment of CM1 with 25 μM DFP and DFO was demonstrated to decrease the levels of the LIP in both cells and tended to reduce the levels of ROS in HepG2 cells. Our findings support the evidence of iron-chelating and free radical-scavenging activities of CM1 in the livers with iron overload, which potentially can protect against oxidative liver inflammation and fibrosis. The efficacy of the CM1 treatment needs to be further investigated intensively under in vivo conditions.