title: Effect of a novel oral active iron chelator: 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) in iron-overloaded and non-overloaded mice.
abstract: OBJECTIVE
  To evaluate efficacy and toxicity of a novel orally active bidentate iron chelator, 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) in mice under normal and iron overload conditions.
  
  
  METHODS
  Wild type C57BL/6 mice were fed with normal and 0.2% (w/w) ferrocene-supplemented (Fe) diets, respectively for 240 d and orally given the CM1 (50, 100 and 200 mg/kg) for 180 d. Blood iron profiles, hematological indices, liver enzymes and histopathology were determined.
  
  
  RESULTS
  CM1 treatment lowered plasma levels of labile plasma iron and non-transferrin bound iron, but not ferritin in the Fe-fed mice. However, the treatment did not impact blood hemoglobin level, white blood cell and platelet numbers in both normal diet and Fe diet-fed mice. Interestingly, CM1 treatment did not markedly elevate plasma aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase activities in the normal diet-fed mice but it tended to increase the levels of the liver enzymes slightly in the Fe-fed mice. Hematoxylin and eosin staining result showed no abnormal pathological changes in heart, liver and spleen tissues.
  
  
  CONCLUSIONS
  It is clear that CM1 would not be toxic to bone marrow and liver cells under normal and iron-overload conditions.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
authors.forename: Nittaya
authors.initials: N
authors.lastname: Chansiw
authors.affiliation: College of Medicine and Public Health, Ubon Ratchathani University, Ubon Ratchathani 34190, Thailand.
authors.forename: Kanjana
authors.initials: K
authors.lastname: Pangjit
authors.affiliation: Institute of Research and Development, Government Pharmaceutical Organization, Ministry of Public Health, Bangkok 10400, Thailand.
authors.forename: Chada
authors.initials: C
authors.lastname: Phisalaphong
authors.affiliation: Department of Haematology, UCL Cancer Institute, Paul O'Gorman Building, 86, Huntley Street, London, WC1E 6BT, United Kingdom.
authors.forename: John B
authors.initials: JB
authors.lastname: Porter
authors.affiliation: Department of Haematology, UCL Cancer Institute, Paul O'Gorman Building, 86, Huntley Street, London, WC1E 6BT, United Kingdom.
authors.forename: Patricia
authors.initials: P
authors.lastname: Evans
authors.affiliation: Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University Salaya Campus, Nakornpathom 73170, Thailand.
authors.forename: Suthat
authors.initials: S
authors.lastname: Fucharoen
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. Electronic address: ssrichai@med.cmu.ac.th.
authors.forename: Somdet
authors.initials: S
authors.lastname: Srichairatanakool
keywords: Iron chelation; Iron overload; Liver enzyme; Thalassemia; Toxicity