铁对所有生物和细胞都是必需的。铁平衡失调的疾病影响着数十亿患者，包括铁超载和其他形式的铁中毒。过多的铁负荷是所有疾病的不良预后因素，可以造成严重的器官损害，并导致许多疾病患者，包括血红蛋白病、造血干细胞移植、骨髓增生异常综合症等，接受慢性红细胞输血后的死亡风险增加。类似的过多体内铁负荷的毒性作用，但疾病进展速度较慢，也存在于特发性多铁血症患者。通过MRI T2*和类似方法，在包括阿尔茨海默病和帕金森病在内的许多神经退行性疾病中，已经通过定位神经成像技术确认了不同脑部区域中过多铁的沉积，其存在怀疑有毒作用。基于铁作为游离自由基反应和芬顿反应的重要生物催化剂的功能，铁也与所有与自由基病理和组织损伤有关的疾病有关。此外，最近发现的铁相关的细胞死亡程序ferroptosis，该程序通过铁的游离自由基产生和细胞膜脂质氧化引发，引发了成千上万的研究，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。此外，还讨论了转变为活性、非蛋白结合形式的铁以及铁与膳食分子如维生素C和多柔比星以及其他异生物分子在致癌和其他形式毒性方面的关系。在每种铁毒性案例和形式中，对机制洞察、诊断标准和分子相互作用的理解对于设计新的有效治疗干预和未来的靶向治疗策略至关重要。特别是基于该方法成功地治疗了大多数铁负荷状况，尤其是通过新的治疗方案将地中海贫血从致命疾病转变为慢性病的过程，完全消除了铁超载和铁中毒。

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.