Suzuki Y, Oda K, Yoshikawa Y, Maeda Y, Suzuki T
Department of Clinical Genetics, Kyushu University, Beppu, Japan.
J Hum Genet. 1999;44(2):79-84. doi: 10.1007/s100380050114.
Alkaptonuria is a rare autosomal recessive disorder characterized by homogentisic aciduria, ochronosis, and arthritis. Although a deficiency of homogentisic acid 1,2-dioxygenase has recently been confirmed at the molecular level, no effective treatment regimen has yet been developed for this disorder. In the present study, 2(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), a potent inhibitor of p-hydroxyphenylpyruvate dioxygenase (which catalyzes the formation of homogentisic acid from p-hydroxyphenylpyruvic acid) was adopted as a possible therapeutic agent for alkaptonuria. NTBC dose-dependently reduced the urinary output of homogentisic acid in a murine model of alkaptonuria that had been created with ethylnitrosourea. These findings suggest that NTBC may be the first potent pharmacotherapeutic agent for alkaptonuria.
黑尿症是一种罕见的常染色体隐性疾病，其特征为尿黑酸尿症、褐黄病和关节炎。尽管最近在分子水平上已证实尿黑酸1,2-双加氧酶缺乏，但尚未针对该疾病开发出有效的治疗方案。在本研究中，采用2(2-硝基-4-三氟甲基苯甲酰基)-1,3-环己二酮（NTBC），一种对羟基苯丙酮酸双加氧酶（催化对羟基苯丙酮酸形成尿黑酸）的强效抑制剂，作为黑尿症可能的治疗药物。在通过乙基亚硝基脲建立的黑尿症小鼠模型中，NTBC剂量依赖性地降低了尿黑酸的尿量。这些发现表明，NTBC可能是第一种用于黑尿症的强效药物治疗剂。
