Evaluation of a novel oral iron chelator 1-(N-acetyl-6-aminohexyl)-3-hydroxypyridin-4-one (CM1) for treatment of iron overload in mice - Advances in Bioscience and Biotechnology

ABB > Vol.4 No.2, February 2013

Evaluation of a novel oral iron chelator 1-(N-acetyl-6-aminohexyl)-3-hydroxypyridin-4-one (CM1) for treatment of iron overload in mice ()

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DOI: 10.4236/abb.2013.42023 5,273 Downloads 9,237 Views Citations

Author(s)

Somdet Srichairatanakool, Kanjana Pangjit, Chada Phisalaphong, Suthat Fucharoen

Affiliation(s)

Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Institute of Research and Development, Government Pharmaceutical Organization, Ministry of Public Health, Bangkok, Thailand.
Thalassemia Research Center, Institute of Molecular Bioscience, Mahidol University Salaya Campus, Nakornpathom, Thailand.

ABSTRACT

Desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX) are promising effective iron chelators for the treatment of iron overload in b-thalassemia patients; nonetheless, their side effects have also been reported. 3-Hydroxypyridinone derivatives are being developed as a safer new chelator and in combined chelation therapy. We evaluated the iron-chelating activity of 1-(N-acetyl-6-aminohexyl)-3-hydroxypyridin-4-one (CM1) in iron-loaded C57BL6 mice. The feeding of a ferrocene-supplemented diet (Fe diet) to mice resulted in iron overload, detectable plasma nontransferrin-bound iron (NTBI) and labile plasma iron (LPI), and increases of red cell membrane iron, plasma malondialdehyde (MDA) and excessive tissue iron deposits. Like DFP, the CM1 lowered the levels of the membrane non-heme iron, the NTBI and LPI (p < 0.05) and the MDA after 3 months of treatment. Administration of the Fe diet and the Fe diet along with the chelators did not change the morphology of the liver and heart. Numerous iron accumulations were observed in the liver and spleen tissues of the Fe dietfed mice, whereas the CM1 reduced such iron deposition. Thus, 1-(N-acetyl-6-aminohexyl)-3-hydro- xypyridin-4-one (CM1) can be considered a candidate bidentate oral iron chelator and is effective in the removal of toxic irons in blood compartment and tissues. The effectiveness and toxicity of the CM1 need to be investigated extensively in thalassemia mice and patients with iron overload.

KEYWORDS

Thalassemia; Iron Overload; Iron Chelator; Hydroxypyridinone; Lipid Peroxidation; Malondialdehyde

Share and Cite:

Srichairatanakool, S. , Pangjit, K. , Phisalaphong, C. and Fucharoen, S. (2013) Evaluation of a novel oral iron chelator 1-(N-acetyl-6-aminohexyl)-3-hydroxypyridin-4-one (CM1) for treatment of iron overload in mice. Advances in Bioscience and Biotechnology, 4, 153-163. doi: 10.4236/abb.2013.42023.

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