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

• Main Authors: Chansiw,N., Pangjit,K., Phisalaphong,C., Porter,J.B., Evans,P.J., Fucharoen,S., Srichairatanakool,S.
• Format: Article
• Published: Elsevier (Singapore) Pte Ltd 2015
• Subjects: Medicine (all)
• Online Access: http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84908174801&origin=inward; http://cmuir.cmu.ac.th/handle/6653943832/38324
• Institution: Chiang Mai University

© 2014 Hainan Medical College. 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.