Stolze K, Nohl H
Institute of Pharmacology and Toxicology, Vet. Med. Univ. of Vienna.
Biochem Pharmacol. 1990 Aug 15;40(4):799-802. doi: 10.1016/0006-2952(90)90318-f.
N. Hydroxyurea forms methemoglobin from oxyhemoglobin with concomitant formation of the aminocarbonylaminooxyl radical H2N-CO-NHO., as detected with electron paramagnetic resonance spectroscopy (EPR). This radical could be detected for several hours in a low steady-state concentration. Approximately 1 hr after the reaction had been started, the EPR spectra of two additional paramagnetic intermediates could be detected at low temperature (77 degrees K), a low-spin ferric methemoglobin complex with hydroxyurea (MetHb-NHOH-CO-NH2) and the hemoglobin-nitric oxide adduct (Hb2(+)-NO). The intensities of their EPR spectra increased steadily over the range of more than 64 hr. The low-spin ferric methemoglobin complex was immediately formed when hydroxyurea was dissolved in a methemoglobin whereas the nitric oxide complex was possibly an oxidation product of the MetHb-hydroxyurea adduct. Its oxidative degradation is known to lead to the very toxic compounds nitric oxide and nitrogen dioxide which can therefore contribute to the toxic action of hydroxyurea.
N - 羟基脲可将氧合血红蛋白转化为高铁血红蛋白，并伴随氨基羰基氨基氧基自由基H2N - CO - NHO·的形成，这可通过电子顺磁共振光谱（EPR）检测到。该自由基可以在低稳态浓度下检测数小时。反应开始约1小时后，在低温（77K）下可检测到另外两种顺磁性中间体的EPR光谱，一种是与羟基脲形成的低自旋铁高铁血红蛋白复合物（MetHb - NHOH - CO - NH2），另一种是血红蛋白 - 一氧化氮加合物（Hb2(+) - NO）。它们的EPR光谱强度在超过64小时的范围内稳步增加。当羟基脲溶解于高铁血红蛋白中时，会立即形成低自旋铁高铁血红蛋白复合物，而一氧化氮复合物可能是MetHb - 羟基脲加合物的氧化产物。已知其氧化降解会产生剧毒化合物一氧化氮和二氧化氮，因此可能导致羟基脲的毒性作用。
