Signorini Lorenzo, Granata Simona, Lupo Antonio, Zaza Gianluigi
Renal Unit, Department of Medicine, University-Hospital of Verona, Verona 37126, Italy.
Int J Mol Sci. 2017 Jul 10;18(7):1481. doi: 10.3390/ijms18071481.
Oxidative stress is a well-described imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense system of cells and tissues. The overproduction of free radicals damages all components of the cell (proteins, lipids, nucleic acids) and modifies their physiological functions. As widely described, this condition is a biochemical hallmark of chronic kidney disease (CKD) and may dramatically influence the progression of renal impairment and the onset/development of major systemic comorbidities including cardiovascular diseases. This state is exacerbated by exposure of the body to uremic toxins and dialysis, a treatment that, although necessary to ensure patients' survival, exposes cells to non-physiological contact with extracorporeal circuits and membranes with consequent mitochondrial and anti-redox cellular system alterations. Therefore, it is undeniable that counteracting oxidative stress machinery is a major pharmacological target in medicine/nephrology. As a consequence, in recent years several new naturally occurring compounds, administered alone or integrated with classical therapies and an appropriate lifestyle, have been proposed as therapeutic tools for CKD patients. In this paper, we reviewed the recent literature regarding the "pioneering" in vivo testing of these agents and their inclusion in small clinical trials performed in patients affected by CKD.
氧化应激是一种已被充分描述的活性氧(ROS)产生与细胞和组织抗氧化防御系统之间的失衡状态。自由基的过度产生会损害细胞的所有成分(蛋白质、脂质、核酸)并改变其生理功能。如广泛描述的那样,这种情况是慢性肾脏病(CKD)的生化标志,可能会显著影响肾功能损害的进展以及包括心血管疾病在内的主要全身性合并症的发生/发展。身体暴露于尿毒症毒素和透析会加剧这种状态,透析虽然是确保患者生存所必需的治疗方法,但会使细胞与体外循环和膜进行非生理性接触,从而导致线粒体和细胞抗氧化还原系统发生改变。因此,不可否认的是,对抗氧化应激机制是医学/肾脏病学中的一个主要药理学靶点。因此,近年来,几种新的天然化合物,单独使用或与传统疗法及适当的生活方式相结合,已被提议作为CKD患者的治疗工具。在本文中,我们回顾了有关这些药物的“开创性”体内试验及其纳入CKD患者小型临床试验的最新文献。