Antioxidants targeting mitochondria function in kidney diseases

Ana Karina Aranda-Rivera , Alfredo Cruz-Gregorio , Isabel Amador-Martínez , Estefani Yaquelin Hernández-Cruz , Edilia Tapia , José Pedraza-Chaverri
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Abstract

Kidney diseases are a growing health problem worldwide, causing millions of deaths. Acute kidney injury (AKI) commonly evolves into chronic kidney disease (CKD) and fibrosis, which is a feature of CKD predisposing to end-stage renal disease. Thus, treatments that avoid this transition are urgently necessary. Mitochondria are the hub energy house of the renal cells, which provides energy in adenosine triphosphate (ATP) form, commonly obtained from β-oxidation through fatty acids degradation into the mitochondrial matrix. Mitochondria are plastic organelles that constantly change according to the cell's energy requirements. For this, mitochondria carry out biogenesis, fission, fusion, and mitophagy/autophagy, processes highly regulated to maintain mitochondrial bioenergetics and homeostasis. Alterations in one or more of these processes might cause detrimental consequences that affect cell function. In this sense, it is widely accepted that mitochondrial dysfunction associated with oxidative stress plays a crucial role in developing kidney diseases. Therefore, antioxidants that target mitochondria might be an excellent strategy to ameliorate mitochondrial dysfunction, and selecting one or another antioxidant could depend on AKI or CKD requirements. This review focuses on potent antioxidants such as sulforaphane (SFN), N-acetyl cysteine (NAC), resveratrol, curcumin, quercetin, and α-mangostin in the improvement of mitochondrial function in kidney pathologies.

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针对肾脏疾病线粒体功能的抗氧化剂
肾脏疾病是全球日益严重的健康问题,导致数百万人死亡。急性肾损伤(AKI)通常会演变成慢性肾病(CKD)和纤维化,而纤维化是慢性肾病的一个特征,容易导致终末期肾病。因此,迫切需要避免这种转变的治疗方法。线粒体是肾脏细胞的能量中心,以三磷酸腺苷(ATP)的形式提供能量,通常通过脂肪酸降解到线粒体基质中的β-氧化作用获得。线粒体是一种可塑性细胞器,会根据细胞的能量需求不断变化。为此,线粒体进行生物生成、裂变、融合和有丝分裂/自噬,这些过程受到高度调控,以维持线粒体的生物能和平衡。其中一个或多个过程的改变可能会造成有害后果,影响细胞功能。从这个意义上讲,人们普遍认为,与氧化应激相关的线粒体功能障碍在肾脏疾病的发生中起着至关重要的作用。因此,针对线粒体的抗氧化剂可能是改善线粒体功能障碍的绝佳策略,而选择一种或另一种抗氧化剂则取决于 AKI 或 CKD 的要求。本综述将重点讨论强效抗氧化剂,如莱菔硫烷(SFN)、N-乙酰半胱氨酸(NAC)、白藜芦醇、姜黄素、槲皮素和α-曼戈斯汀在改善肾脏病变线粒体功能方面的作用。
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