Manion C V, Howard J, Ogle B, Parkhurst J, Edmundson A
Department of Clinical Pharmacology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73112, USA.
Clin Pharmacol Ther. 2001 May;69(5):346-55. doi: 10.1067/mcp.2001.115141.
To examine the in vitro and in vivo attributes of aspartame and to determine its efficacy for treating sickle cell anemia.
Aspartame (l-aspartyl-l-phenylalanine methyl ester) binds with 2 human Bence Jones proteins. The proteins (Mcg and Sea) showed phenylalanine penetrating into hydrophobic binding sites. This aspartame property suggested a potential to interfere with sickle hemoglobin fibril formation.
For the in vitro studies, blood from 20 subjects monitored for sickle cell anemia was collected in heparinized tubes. Specimens were divided in thirds and aspartame was added to 2 tubes to yield a 1 mg/mL or 2 mg/mL concentration. Sickled cells that were present after a drop from each aliquot was added to a fresh 2% metabisulfite solution were counted 3 times. For the in vivo studies, 23 subjects from the Sickle Cell Clinic (University of Oklahoma Health Sciences Center, Oklahoma City, Okla) consented to participate in a randomized single-dose administration of 1.5, 3.0, or 6 mg/kg aspartame. Heparinized blood was obtained at 0, 30, 60, 120, 240, 480, and 1440 minutes after aspartame administration. Specimens were counted in a blinded manner by means of the technique used for the in vitro method, but a photomicrograph of 1 field from each triplicate count was made. The pictures were marked and were computer counted.
For the in vitro studies, sickled cells decreased from 28% to < 14% when 1 mg/mL aspartame was added and decreased further with 2 mg/mL. For the in vivo studies, a decreased number of sickled cells in homozygous blood (HbSS) were observed after oral administration of aspartame. Sickling was inhibited by 6 mg/kg aspartame for at least 6 hours in 15 subjects with HbSS anemia.
Further evaluations of the efficacy of aspartame for sickle crisis and crisis prevention appears to be warranted.
研究阿斯巴甜的体外和体内特性，并确定其治疗镰状细胞贫血的疗效。
阿斯巴甜（L-天冬氨酰-L-苯丙氨酸甲酯）与两种人本周氏蛋白结合。这些蛋白（Mcg和Sea）显示苯丙氨酸渗入疏水结合位点。阿斯巴甜的这一特性表明其有可能干扰镰状血红蛋白纤维的形成。
在体外研究中，将20名镰状细胞贫血监测对象的血液采集到肝素化管中。样本分成三等份，向其中两管中加入阿斯巴甜，使其浓度达到1mg/mL或2mg/mL。从每份等分试样中取出一滴加入新鲜的2%偏重亚硫酸盐溶液后出现的镰状细胞计数3次。在体内研究中，来自镰状细胞诊所（俄克拉荷马大学健康科学中心，俄克拉荷马城，俄克拉荷马州）的23名受试者同意参与一项随机单剂量给药研究，给予1.5、3.0或6mg/kg的阿斯巴甜。在给予阿斯巴甜后的0、30、60、120、240、480和1440分钟采集肝素化血液。样本采用与体外方法相同的技术进行盲法计数，但对每次重复计数的1个视野拍摄显微照片。照片做好标记后进行计算机计数。
在体外研究中，加入1mg/mL阿斯巴甜时，镰状细胞从28%降至<14%，加入2mg/mL时进一步下降。在体内研究中，口服阿斯巴甜后，纯合血（HbSS）中的镰状细胞数量减少。在15名HbSS贫血患者中，6mg/kg的阿斯巴甜可使镰状化至少抑制6小时。
阿斯巴甜对镰状细胞危象及预防危象的疗效似乎有必要进行进一步评估。
