Wang Y M, Patterson J H, Van Eys J
J Clin Invest. 1971 Jul;50(7):1421-8. doi: 10.1172/JCI106625.
NADP-linked xylitol dehydrogenase has been found to be present in human red blood cells. This enzyme activity is normal in most glucose-6-phosphate dehydrogenase (G6PD)-deficient red cells. Xylitol was explored as a potential agent for treatment of hemolysis in patients with G6PD-deficiency. Intracellular GSH (glutathione, reduced) was first converted to its oxidized form by incubation of the erythrocytes with acetylphenylhydrazine or by pretreatment with methyl phenyldiazenecarboxylate. The addition of 0.15 M xylitol was shown to be more effective than 0.15 M glucose in maintaining the levels of GSH in G6PD-deficient red cells during such oxidative challenge. Rabbit erythrocytes contain less activity of G6PD and glutathione reductase compared with the normal human adult values, but have an active xylitol dehydrogenase. The rabbit erythrocyte is sensitive to acetylphenylhydrazine and primaquine phosphate. In both in vivo and in vitro experiments, xylitol was found to partially prevent acetylphenylhydrazine induced acute hemolysis of the rabbit red cell and GSH content was found to be preserved. The intravenous injection of xylitol (0.5 g/kg body weight per 6 hr) for 6 days, seemed to be nontoxic to the animal. The results suggest that xylitol should be further investigated as an agent for the treatment of G6PD-deficient patients during acute hemolytic episodes.
已发现烟酰胺腺嘌呤二核苷酸磷酸(NADP)连接的木糖醇脱氢酶存在于人类红细胞中。在大多数葡萄糖-6-磷酸脱氢酶(G6PD)缺乏的红细胞中,这种酶的活性是正常的。木糖醇被作为治疗G6PD缺乏症患者溶血的潜在药物进行了研究。通过将红细胞与乙酰苯肼孵育或用甲基苯基重氮羧酸酯预处理,细胞内的谷胱甘肽(GSH,还原型)首先被转化为其氧化形式。在这种氧化应激期间,添加0.15M木糖醇在维持G6PD缺乏的红细胞中GSH水平方面比添加0.15M葡萄糖更有效。与正常成年人相比,兔红细胞中G6PD和谷胱甘肽还原酶的活性较低,但具有活跃的木糖醇脱氢酶。兔红细胞对乙酰苯肼和磷酸伯氨喹敏感。在体内和体外实验中,均发现木糖醇可部分预防乙酰苯肼诱导的兔红细胞急性溶血,且GSH含量得以保留。静脉注射木糖醇(每6小时0.5g/kg体重),持续6天,对动物似乎无毒。结果表明,木糖醇应作为治疗急性溶血发作期间G6PD缺乏患者的药物进一步研究。