Mechanism on hemolytic anemia induced by phenylhydrazine

苯肼与红细胞中的血红蛋白反应，产生亨氏小体沉淀，引起溶血。大量的研究工作致力于了解导致亨氏小体形成的过程，这与血红蛋白的不可逆氧化变性有关。在苯肼与氧合血红蛋白的体外反应中，检测到N-苯基原卟啉，证明了血红素的修饰。用苯肼给大鼠灌胃，从实验动物体内分离出苯基化的卟啉，研究其体内血红素的苯基化作用。用酸性甲醇和锌离子溶液处理大鼠的血液和脾，分离出一种绿色色素。用薄层层析法将色素分解成I和II两种组分。颜料I是酯化的N-苯基原卟啉IX锌络合物的两个异构体的混合物，其中含有乙烯基取代的吡咯环A和…更多的B被苯基化，颜料II是丙酸取代环C和D上N-苯基的卟啉配合物的两个异构体的混合物。氧合血红蛋白和苯肼反应产生的苯基在血红素铁上反应生成苯基络合物，颜料是通过有氧处理苯基从铁迁移到吡咯氮而形成的，用于分离颜料的酸性甲醇。因此，苯肼处理的大鼠的血液中必须含有含铁苯基的血红蛋白。外源性的苯基大配体插入到血红蛋白的血红素口袋中，有望改变接触，导致血红蛋白分子的不稳定。通过苯肼与氧合血红蛋白的反应，该分子降低了其对伴随苯基产生的氧化剂的抗氧化性，并导致变性形成亨氏小体。在处理大鼠体内检测到修饰的血红素为苯肼的作用机制提供了一种现象的解释。较少

Phenylhydrazine reacts with hemoglobin in erythrocytes to produce the precipitation of Heinz body which induces hemolysis. A significant amount of research effort has been devoted to understanding the process leading to Heinz body formation, which is associated with irreversible oxidative denaturation of hemoglobin. Heme modification has been demonstrated by the detection of N-phenylated protoporphyrin in the in vitro reaction of phenylhydrazine with oxyhemoglobin. In this paper, phenylhydrazine was given to rat, and the in vivo phenylation of heme of hemoglobin was examined with the isolation of the phenylated porphyrin from the treated animal. The blood and the spleen of the rat were treated with a solution of acidic methanol and zinc ion to isolate a green pigment. The pigment was resolved into the two, I and II, by thin layer chromatography. Pigment I was a mixture of two isomers of zinc complex of esterified N-phenylprotoporphyrin IX, in which vinyl-substituted pyrrole rings A and … More B were phenylated, and pigment II was a mixture of two isomers of the porphyrin complex with the N-phenyl group on propionic acid-substituted rings C and D.Phenyl radical produced by the reaction of oxyhemoglobin with phenylhydrazine reacts at heme iron to form the phenyliron complex, and the pigments are formed by the migration of the phenyl group from the iron to the pyrrole nitrogen by aerobic treatment with acidic methanol used for the isolation of pigments. Thus, the blood of the phenylhydrazine-treated rat must contain hemoglobin with iron-phenyl heme.The insertion of exogenous large ligand of phenyl group to the heme pocket of hemoglobin is expected to alter the contact to lead to destabilization of hemoglobin molecule. The molecule diminishes its resistance to oxidation by oxidants produced concomitantly with phenyl radical by the reaction of phenylhydrazine with oxyhemoglobin, and is led to denaturation to form Heinz bodies. The detection of the modified heme in the treated rat provides a phenomenon for the proposed mechanism for phenylhydrazine action to explain. Less