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
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
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DOI：
10.1016/s1995-7645(14)60223-6
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发表时间：
2014-09-01
影响因子：
3.1
通讯作者：
Srichairatanakool, Somdet
中科院分区：
文献类型：
--
作者：
Chansiw, Nittaya;Pangjit, Kanjana;Srichairatanakool, Somdet
目的：评价一种新型口服活性双齿铁螯合剂1-（N-乙酰基-6-氨基己基）-3-羟基-2-甲基吡啶-4-酮（CM 1）在正常和铁过载条件下的小鼠中的作用。野生型C57 BL/6小鼠分别用正常和添加0.2%（w/w）二茂铁（Fe）的饲料喂养240 d，并经口给予CM 1（50、100和200 mg/kg）连续给药180 d。血铁配置文件，血液学指标，肝酶和组织病理学进行了determined.Results：CM 1治疗降低不稳定的血浆铁和非转铁蛋白结合铁的血浆水平，但不铁蛋白在铁喂养的小鼠。然而，在正常饮食和Fe饮食喂养的小鼠中，该处理不影响血液血红蛋白水平、白色血细胞和血小板数量。有趣的是，CM 1治疗并没有显着提高血浆天冬氨酸转氨酶，丙氨酸转氨酶和碱性磷酸酶的活动在正常饮食喂养的小鼠，但它往往会增加肝酶的水平略有铁喂养的小鼠。结论：CM 1在正常和铁超载条件下对骨髓和肝细胞无毒性作用。
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.