Postgraduate Research Institute of Science, Technology, Environment and Medicine, 3, Ammochostou Street, Limassol 3021, Cyprus.
Int J Mol Sci. 2023 Aug 18;24(16):12928. doi: 10.3390/ijms241612928.
Iron is essential for all organisms and cells. Diseases of iron imbalance affect billions of patients, including those with iron overload and other forms of iron toxicity. Excess iron load is an adverse prognostic factor for all diseases and can cause serious organ damage and fatalities following chronic red blood cell transfusions in patients of many conditions, including hemoglobinopathies, myelodyspasia, and hematopoietic stem cell transplantation. Similar toxicity of excess body iron load but at a slower rate of disease progression is found in idiopathic haemochromatosis patients. Excess iron deposition in different regions of the brain with suspected toxicity has been identified by MRI T2* and similar methods in many neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Based on its role as the major biological catalyst of free radical reactions and the Fenton reaction, iron has also been implicated in all diseases associated with free radical pathology and tissue damage. Furthermore, the recent discovery of ferroptosis, which is a cell death program based on free radical generation by iron and cell membrane lipid oxidation, sparked thousands of investigations and the association of iron with cardiac, kidney, liver, and many other diseases, including cancer and infections. The toxicity implications of iron in a labile, non-protein bound form and its complexes with dietary molecules such as vitamin C and drugs such as doxorubicin and other xenobiotic molecules in relation to carcinogenesis and other forms of toxicity are also discussed. In each case and form of iron toxicity, the mechanistic insights, diagnostic criteria, and molecular interactions are essential for the design of new and effective therapeutic interventions and of future targeted therapeutic strategies. In particular, this approach has been successful for the treatment of most iron loading conditions and especially for the transition of thalassemia from a fatal to a chronic disease due to new therapeutic protocols resulting in the complete elimination of iron overload and of iron toxicity.
铁是所有生物和细胞所必需的。铁失衡疾病影响着数十亿患者，包括铁过载和其他形式的铁毒性患者。过量的铁负荷是所有疾病的不良预后因素，可导致许多疾病患者发生严重的器官损伤和死亡，这些疾病包括血红蛋白病、骨髓增生异常和造血干细胞移植。在特发性血色病患者中，也会发现由于慢性红细胞输注导致的身体铁负荷过量但疾病进展速度较慢的类似毒性。在许多神经退行性疾病中，包括阿尔茨海默病和帕金森病，通过 MRI T2* 和类似方法已经在大脑的不同区域发现了具有潜在毒性的过量铁沉积。基于其作为自由基反应和 Fenton 反应主要生物催化剂的作用，铁也与所有与自由基病理和组织损伤相关的疾病有关。此外，最近发现的铁死亡是一种基于铁和细胞膜脂质氧化自由基生成的细胞死亡程序，这引发了数千项研究，并将铁与心脏、肾脏、肝脏和许多其他疾病（包括癌症和感染）联系起来。不稳定的、非蛋白结合形式的铁及其与膳食分子（如维生素 C）和药物（如阿霉素和其他异生物质分子）的复合物的毒性影响与致癌作用和其他形式的毒性有关。在每种铁毒性的情况下和形式中，机制见解、诊断标准和分子相互作用对于设计新的和有效的治疗干预措施以及未来的靶向治疗策略都是至关重要的。特别是，这种方法在治疗大多数铁负荷情况方面取得了成功，特别是在由于新的治疗方案导致铁过载和铁毒性完全消除，从而使地中海贫血从致命疾病转变为慢性疾病方面取得了成功。
