このエントリーをはてなブックマークに追加
ID 32823
JaLCDOI
FullText URL
Author
Nakanishi, Akira
Kinuta, Keiko
Abe, Tadashi
Araki, Kenta
Yoshida, Yumi
Liang, Shuang
Li, Shun-Ai
Kinuta, Masahiro
Abstract

Administration of phenylhydrazine to rabbits resulted in the denaturation of hemoglobins in erythrocytes, causing the formation of intracellular precipitates known as Heinz bodies, severe hemolytic anemia, and reticulocytosis. To elucidate the molecular mechanism of the destabilization, we allowed human oxyhemoglobins to react aerobically with phenylhydrazine. After treatment with acetic acid/HCl and H2SO4/methanol, the chloroform extract contained blue-green pigments of major products accompanied by different minor products. Each product was isolated by column chromatography. By fast-atom-bombardment mass spectrometry (FAB-MS) and proton nuclear magnetic resonance (1H-NMR) spectrometry, dimethyl esters of N-phenylprotoporphyrin IX and meso, N-diphenylprotoporphyrin IX were determined. Other major products also were determined to be dimethyl esters of triphenyl-and tetraphenyl-substituted protoporphyrins by FAB-MS. The formation of meso, N-diphenylprotoporphyrin indicated that the addition of a phenyl radical to the meso-carbon atom of the protoporphyrin ring occurred. Triphenyl and tetraphenyl adducts also indicated the formation of phenyl radicals in the aerobic reaction of phenylhydrazine with oxyhemoglobins. From these results, we suggest that the formation of phenyl radicals and the replacement of heme with phenyl-substituted protoporphyrins cause the destabilization of hemoglobins to induce Heinz bodies and hemolytic anemia with phenylhydrazine.

Keywords
phenylhydrazine
hemoglobin
protoporphyrin
fast-atom-bombardment mass spectrometry(FAB-MS)
proton nuclear magnetic resonance(H-NMR)spectrometry
Amo Type
Article
Published Date
2003-10
Publication Title
Acta Medica Okayama
Volume
volume57
Issue
issue5
Publisher
Okayama University Medical School
Start Page
249
End Page
256
ISSN
0386-300X
NCID
AA00508441
Content Type
Journal Article
language
英語
File Version
publisher
Refereed
True
PubMed ID
Web of Sience KeyUT