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

Nittaya Chansiw; Somdet Srichairatanakool; Kanjana Pangjit; Chada Phisalaphong; John B Porter; Patricia Evans; Suthat Fucharoen

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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

Author: Nittaya CHANSIW ¹ ; Somdet SRICHAIRATANAKOOL ¹ ; Kanjana PANGJIT ² ; Chada PHISALAPHONG ³ ; John B. PORTER ⁴ ; Patricia EVANS ⁴ ; Suthat FUCHAROEN ⁵
Author Information

1. Department of Biochemistry, Faculty of Medicine, Chiang Mai University
2. College of Medicine and Public Health, Ubon Ratchathani University
3. Institute of Research and Development, Government Pharmaceutical Organization, Ministry of Public Health
4. Department of Haematology, UCL Cancer Institute
5. Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University Salaya Campus
Publication Type:Journal Article
Keywords: Iron chelation; Iron overload; Liver enzyme; Thalassemia; Toxicity
From: Asian Pacific Journal of Tropical Medicine 2014;7(S1):S155-S161
CountryChina
Language:Chinese
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.