Supplemental Digital Content is available in the text. Preeclampsia is a multifactorial hypertensive disorder of pregnancy founded on abnormal placentation, and the resultant placental ischemic microenvironment is thought to play a crucial role in its pathophysiology. Placental ischemia because of fluctuations in the delivery of oxygen results in oxidative stress, and recent evidence suggests that mitochondrial dysfunction may be a prime mediator. However, large clinical trials of therapeutic antioxidants such as vitamins C and E for the treatment of preeclampsia have been disappointing. L-(+)-ergothioneine (ERG)—an unusual amino acid betaine derived from histidine—has important cytoprotective and antioxidant properties under conditions of high oxidative stress. In this study, we investigated the potential therapeutic effects of administration of ERG in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. ERG (25 mg/kg per day) was administered to rats on gestational day 11. On gestational day 14, RUPP surgery was performed, and on gestational day 19, blood pressure (mean arterial pressure) and fetal growth were measured. Production of mitochondria-specific H2O2 was analyzed in vivo in kidney samples. ERG ameliorated the hypertension (129±3 versus 115±4 mm Hg; P=0.01; n=8) and significantly increased pup weight in RUPP rats. ERG also significantly decreased circulating levels of antiangiogenic sFlt-1 (soluble fms-like tyrosine kinase-1) in RUPP rats (1367±245 pg/mL; P=0.04). Mitochondria-specific H2O2 (0.022±0.003 versus 0.029±0.001; MitoP/B ratio, n=3; P=0.05) was also significantly decreased in kidney tissue in RUPP rats treated with ERG. These data support the potential use of ERG for the treatment of preeclampsia.

中文翻译：

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L-(+)-麦角硫因显着改善降低子宫灌注压大鼠模型先兆子痫的临床特征

补充数字内容在文本中可用。先兆子痫是一种以胎盘异常为基础的多因素妊娠高血压疾病，由此产生的胎盘缺血微环境被认为在其病理生理学中起关键作用。由于氧输送波动导致的胎盘缺血导致氧化应激，最近的证据表明线粒体功能障碍可能是主要介质。然而，用于治疗先兆子痫的治疗性抗氧化剂（如维生素 C 和 E）的大型临床试验令人失望。L-(+)-麦角硫因 (ERG)——一种源自组氨酸的不寻常的氨基酸甜菜碱——在高氧化应激条件下具有重要的细胞保护和抗氧化特性。在这项研究中，我们研究了 ERG 在降低子宫灌注压 (RUPP) 大鼠先兆子痫模型中的潜在治疗效果。在妊娠第 11 天给予大鼠 ERG（每天 25 毫克/千克）。在妊娠第 14 天，进行 RUPP 手术，并在妊娠第 19 天测量血压（平均动脉压）和胎儿生长。在肾脏样本中体内分析了线粒体特异性 H2O2 的产生。ERG 改善了高血压（129±3 与 115±4 mm Hg；P=0.01；n=8）并显着增加了 RUPP 大鼠的幼仔体重。ERG 还显着降低了 RUPP 大鼠中抗血管生成 sFlt-1（可溶性 fms 样酪氨酸激酶-1）的循环水平（1367±245 pg/mL；P=0.04）。线粒体特异性 H2O2（0.022±0.003 对 0.029±0.001；MitoP/B 比率，n=3；P=0。05) 在用 ERG 治疗的 RUPP 大鼠的肾组织中也显着降低。这些数据支持 ERG 用于治疗先兆子痫的潜在用途。