Someya Tomonosuke, Kaneko Kazunari, Yamada Toshiyuki, Yamashiro Yuichiro
Department of Pediatrics, School of Medicine, Juntendo University, Tokyo, Japan.
Pediatr Nephrol. 2005 Oct;20(10):1430-4. doi: 10.1007/s00467-005-1959-9. Epub 2005 Aug 4.
Recent studies indicate that excessive production of oxidants plays a role in the pathogenesis of glomerular injury leading to proteinuria in patients with minimal-change nephrotic syndrome (MCNS). The novel free radical scavenger, edaravone (EDA), which was recently developed in Japan, is currently used in patients with stroke. We studied whether this new agent would be beneficial in patients with MCNS by its antioxidant activity and examined its effect on proteinuria in nephrosis induced by puromycin-aminonucleoside (PAN) in rats. Nineteen Wistar-Kyoto rats injected with PAN were assigned to four groups: group 1, without EDA (n=4); group 2, concomitant EDA injection from 1 day prior to PAN administration (n=5); group 3, concomitant EDA injection from 1 day after PAN administration (n=5); group 4, concomitant EDA injection from 3 days after PAN administration (n=5). Daily urinary excretions of protein and 8-hydroxy-2'-deoxyguanosine (8-OHdG), a new sensitive marker of oxidative DNA damage in vivo, were measured in each group from the 1st to the 30th day after PAN injection. In group 1 proteinuria developed from the 5th day and reached the peak level on the 9th day. In groups 2, 3, and 4 proteinuria did not appear until the 6th day. The excretions in urinary protein and 8-OHdG were significantly lower in groups 2, 3, and 4 than group 1 on days 5, 9, and 25. In conclusion, EDA could delay and ameliorate the urinary protein excretion in accordance with the urinary 8-OHdG excretion in PAN-induced nephrosis.
最近的研究表明，氧化剂的过度产生在微小病变肾病（MCNS）患者导致蛋白尿的肾小球损伤发病机制中起作用。新型自由基清除剂依达拉奉（EDA）最近在日本研发出来，目前用于中风患者。我们研究了这种新药因其抗氧化活性对MCNS患者是否有益，并检测了其对嘌呤霉素-氨基核苷（PAN）诱导的大鼠肾病蛋白尿的影响。19只注射PAN的Wistar-Kyoto大鼠被分为四组：第1组，不使用EDA（n = 4）；第2组，在给予PAN前1天开始同时注射EDA（n = 5）；第3组，在给予PAN后1天开始同时注射EDA（n = 5）；第4组，在给予PAN后3天开始同时注射EDA（n = 5）。从注射PAN后的第1天到第30天，测量每组大鼠每天的尿蛋白和8-羟基-2'-脱氧鸟苷（8-OHdG，体内氧化性DNA损伤的一种新的敏感标志物）排泄量。在第1组中，蛋白尿从第5天开始出现，并在第9天达到峰值水平。在第2、3和4组中，蛋白尿直到第6天才出现。在第5、9和25天，第2、3和4组的尿蛋白和8-OHdG排泄量明显低于第1组。总之，在PAN诱导的肾病中，依达拉奉可根据尿8-OHdG排泄量延迟并改善尿蛋白排泄。
