Vaka Ramana, Deer Evangeline, LaMarca Babbette
Center for Excellence in Cardiovascular and Renal Research, Department of Pharmacology, Physiology & Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Center for Excellence in Cardiovascular and Renal Research, Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Antioxidants (Basel). 2022 Jan 22;11(2):210. doi: 10.3390/antiox11020210.
Despite considerable research efforts over the past few decades, the pathology of preeclampsia (PE) remains poorly understood with no new FDA-approved treatments. There is a substantial amount of work being conducted by investigators around the world to identify targets to develop therapies for PE. Oxidative stress has been identified as one of the crucial players in pathogenesis of PE and has garnered a great deal of attention by several research groups including ours. While antioxidants have shown therapeutic benefit in preclinical models of PE, the clinical trials evaluating antioxidants (vitamin E and vitamin C) were found to be disappointing. Although the idea behind contribution of mitochondrial oxidative stress in PE is not new, recent years have seen an enormous interest in exploring mitochondrial oxidative stress as an important pathological mediator in PE. We and others using animals, cell models, and preeclamptic patient samples have shown the evidence for placental, renal, and endothelial cell mitochondrial oxidative stress, and its significance in PE. These studies offer promising results; however, the important and relevant question is can we translate these results into clinical efficacy in treating PE. Hence, the purpose of this review is to review the existing literature and offer our insights on the potential of mitochondrial antioxidants in treating PE.
尽管在过去几十年里进行了大量研究，但先兆子痫（PE）的病理机制仍未得到充分理解，且尚无新的获得美国食品药品监督管理局（FDA）批准的治疗方法。世界各地的研究人员正在开展大量工作，以确定开发PE治疗方法的靶点。氧化应激已被确定为PE发病机制中的关键因素之一，并受到包括我们在内的多个研究团队的广泛关注。虽然抗氧化剂在PE的临床前模型中显示出治疗益处，但评估抗氧化剂（维生素E和维生素C）的临床试验结果却令人失望。尽管线粒体氧化应激在PE中的作用这一观点并不新颖，但近年来，人们对探索线粒体氧化应激作为PE重要病理介质的兴趣大增。我们和其他研究人员利用动物、细胞模型和先兆子痫患者样本，已经证明了胎盘、肾脏和内皮细胞线粒体氧化应激的存在及其在PE中的重要性。这些研究提供了有前景的结果；然而，重要且相关的问题是，我们能否将这些结果转化为治疗PE的临床疗效。因此，本综述的目的是回顾现有文献，并就线粒体抗氧化剂治疗PE的潜力提供我们的见解。
