Impact of intravenous iron on cardiac and skeletal oxidative stress and cardiac mitochondrial function in experimental uraemia chronic kidney disease
Impact of intravenous iron on cardiac and skeletal oxidative stress and cardiac mitochondrial function in experimental uraemia chronic kidney disease
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DOI：
10.52586/4958
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发表时间：
2021-09-30
影响因子：
3.1
通讯作者：
Bhandari, Sunil
中科院分区：
文献类型：
--
作者：
Bhandari, Sunil
简介：尿毒症会导致心脏结构的变化、代谢重塑和贫血，这是慢性肾病患者发生心力衰竭的关键因素。先前的研究已经发现线粒体功能异常，可能会损害能量供应并增强氧化应激。这项研究描述了尿毒症患者的氧化状态和线粒体功能的变化，以及通过静脉补铁治疗纠正贫血的影响。方法：通过肾次全切除术和术后 6 周肠外注射铁剂，在雄性 Sprague-Dawley 大鼠中诱发实验性尿毒症。通过测量补充或不补充铁的假手术动物和尿毒症动物的促氧化活性和抗氧化能力来评估组织样品的氧化应激。测量了硫代巴比妥酸反应物质（TBARS）、乌头酸酶活性和心磷脂。使用 Seahorse XFp 分析仪对从心脏组织切下的分离线粒体进行线粒体功能评估。结果：该尿毒症模型中心脏组织的氧化应激增加（GSSG/GSH 比率、TBARS 增加和促氧化酶活性增加）。对骨骼组织没有影响。肠外铁通过增强心脏组织和骨骼组织的抗氧化防御系统来改善氧化应激。对心脏线粒体呼吸储备的检查表明，肠外铁恢复了线粒体功能。该尿毒症实验模型证明了心肌存在特定的氧化应激，但骨骼氧化状态没有显着变化。铁疗法改善了抗氧化防御系统，从而减少了心脏和骨骼组织的氧化应激。心脏线粒体功能有所改善。结论：该实验证据表明，铁疗法可以降低氧化应激的脆弱性，并可能通过改善线粒体功能来改善心脏和骨骼功能。
Introuction: Uraemia leads to changes in car-diac structure, metabolic remodeling and anaemia, key fac-tors in the development of heart failure in patients with chronic kidney disease. Previous studies have identified abnormalities in mitochondrial function, potentially impair-ing energy provision and enhancing oxidative stress. This study characterised oxidant status and changes in mito-chondrial function in uraemia and the impact of correcting anaemia via intravenous iron therapy. Methods: Experi-mental uraemia was induced in male Sprague-Dawley rats via a subtotal nephrectomy and parenteral iron administra-tion given 6 weeks post-surgery. Oxidative stress from tis-sue samples was evaluated by measuring pro-oxidant activ-ities and anti-oxidant capacities in both sham and uraemic animals with and without iron supplementation. Thiobar-bituric acid-reactive substances (TBARS), aconitase activ-ity and cardiolipin were measured. Mitochondrial function was assessed using the Seahorse XFp analyser on isolated mitochondria excised from cardiac tissue. Results: Oxida-tive stress in this uraemic model was increased in cardiac tissue (increased GSSG/GSH ratio, TBARS and increased activities of pro-oxidant enzymes). There was no impact on skeletal tissue. Parenteral iron ameliorated oxidative stress by enhancing the anti-oxidant defense system in cardiac tis-sue and skeletal tissue. Examination of respiratory reserve in cardiac mitochondria demonstrated that parenteral iron restored mitochondrial function. This experimental model of uraemia demonstrated a specific oxidative stress on the heart muscle without significant changes in skeletal oxi-dant status. Iron therapy improved anti-oxidant defence system, consequently reducing oxidative stress in the heart and skeletal tissue. There was an improvement in cardiac mitochondrial function. Conclusions: This experimental evidence indicates that iron therapy could reduce vulnera-bility to oxidative stress and potentially improve both car-diac and skeletal functional capacity from improvements in mitochondrial function.