Mechanism on hemolytic anemia induced by phenylhydrazine

苯肼致溶血性贫血的机制

• 批准号: 60571044
• 负责人: HIROTA Kazuhiro
• 金额: $ 1.09万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1986
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-60571044/
• 关键词: Phenylhydrazine; Hemolysis; Hemoglobin; 赤血球

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

苯肼与红细胞中的血红蛋白反应，产生海因茨小体沉淀，引起溶血。大量的研究工作致力于了解导致海因茨小体形成的过程，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，通过检测N-苯基化原卟啉，证明了血红素的修饰。本文用苯肼处理大鼠，从处理后的动物体内分离出苯基卟啉，研究血红蛋白中血红素的苯基化。用酸性甲醇和锌离子的溶液处理大鼠的血液和脾脏，以分离绿色色素。通过薄层色谱法将色素分解为两种，I和II。颜料I是酯化的N-苯基原卟啉IX的锌络合物的两种异构体的混合物，其中乙烯基取代的吡咯环A和 ...更多信息 B被苯基化，颜料II是在丙酸取代的环C和D上具有N-苯基的卟啉络合物的两种异构体的混合物。由氧合血红蛋白与苯肼反应产生的苯基自由基与血红素铁反应形成苯基铁络合物，并且通过用用于制备的酸性甲醇进行有氧处理，通过苯基从铁迁移到吡咯氮而形成颜料。分离色素。因此，苯肼处理的大鼠的血液中一定含有铁-苯基血红素的血红蛋白，将外源性苯基大配体插入血红蛋白的血红素口袋中，预期会改变接触，导致血红蛋白分子的不稳定。该分子通过苯肼与氧合血红蛋白反应产生的氧化剂与苯基自由基一起降低其抗氧化性，并导致变性形成海因茨体。在处理的大鼠中检测到修饰的血红素为苯肼作用的拟议机制提供了一个现象来解释。少

项目成果

Kazuhiro Hirota, Tadashi Hatanaka, and Takashi Hirota: "Isolation of N-phenylporphyrin IX from the red cells and spleen of the phenylhydrazine-treated rat" Archives of Biochemistry and Biophysics. (1987)

Kazuhiro Hirota、Tadashi Hatanaka 和 Takashi Hirota：“从苯肼处理的大鼠的红细胞和脾中分离 N-苯基卟啉 IX”生物化学和生物物理学档案。

広田和弘,畑中唯史,広田喬: Archives of Biochemistry and Biophysics. (1987)

Kazuhiro Hirota、Yuji Hatanaka、Takashi Hirota：生物化学和生物物理学档案（1987）。