OXIDATION OF AGRANULOCYTOSIS CAUSING DRUGS BY MYELOPEROXIDASE

髓过氧化物酶，一种丰富的中性粒细胞蛋白，参与微生物 致死和炎症组织损伤，能够氧化生物 在过氧化氢存在下的分子和药物。所需的过氧化氢是 作为呼吸爆发的副产品在体内供应。 次氯酸(HOCl)也是一种强有力的氧化剂，可以在 髓过氧化物酶、过氧化氢和氯离子的存在。 OPC-8212是目前正在临床应用的一种新型正性肌力药。 在美国用于治疗充血性心力衰竭的试验。在……里面 以前的试验表明，OPC-8212与粒细胞缺乏症的发病有关 在接受药物治疗的患者中有14%。在那些表现出 粒细胞缺乏症的迹象，75%的人接种过流感疫苗 就在审判之前或期间，这可能刺激了 中性粒细胞。为了探测这个系统，EPR(电子顺磁共振) 光谱学)和氧气摄取量。以澄清它是否 是髓过氧化物酶导致这种药物的氧化还是 二次氧化剂，次氯酸，两种缓冲体系，一种磷酸盐 不含氯离子的缓冲液和磷酸盐缓冲液 使用的是溶液。

Myeloperoxidase, an abundant neutrophil protein involved in microbial killing and inflammatory tissue damage, is capable of oxidizing biological molecules and drugs in the presence of H2O2. The required H2O2 is supplied in vivo as a secondary product of the respiratory burst. Hypochlorous acid (HOCl) is also a potent oxidant and can be formed in the presence of myeloperoxidase, H2O2 and Cl-. OPC-8212 is a new positive inotropic agent currently undergoing clinical trials in the US for use in the treatment of congestive heart failure. In previous trials, OPC-8212 has been linked to the onset of agranulocytosis in 14% of the patients receiving the drug. Of those patients displaying signs of agranulocytosis, 75% had received an influenza vaccine either just prior to or during the trial, which may have stimulated the neutrophils. To probe this system, EPR (electron paramagnetic resonance spectroscopy) and oxygen uptake will be used. To elucidate whether it is the myeloperoxidase responsible for the oxidation of this drug or the secondary oxidant, hypochlorous acid, two buffer systems, a phosphate buffer containing no chloride ions and a phosphate buffered saline solution were used.