Park So-Hyun, Song Soo-Jin, Lee Jin-A, Shin Jung-A
Department of Anatomy, Ewha Womans University College of Medicine, Seoul, South Korea.
Department of Urology, Ewha Womans University Seoul Hospital, Seoul, South Korea.
J Gastroenterol Hepatol. 2025 Apr;40(4):1016-1025. doi: 10.1111/jgh.16908. Epub 2025 Feb 19.
Although iron is a vital component in the body, excessive iron leads to iron toxicity, which affects vital organs. In particular, the liver is considerably affected by iron toxicity because it stores the highest amount of iron in the body. Nonetheless, the relationship between iron overload and aging in the liver has not yet been clearly identified. This study aimed to observe the effects of aging on iron overload in the liver. Female C57BL/6J mice were randomly divided into vehicle control and iron overload groups (n = 7-22 per group). The iron overload group was injected with iron-dextran (Fe-dextran, ferric hydroxide dextran complex) (0.5 g/kg) for 4 weeks. After the experimental period, liver and blood samples were obtained from 2-, 15-, and 22-month-old mice. Liver weight, iron deposition, structural changes, cell death, extracellular matrix deposition, and fenestration of sinusoidal vessels were analyzed and compared between the groups. Additionally, biochemical analyses (aspartate aminotransferase, alanine aminotransferase, and serum total iron levels) were performed. The iron overload group exhibited significant differences compared with the control group with age. In the elderly iron overload model, iron deposition, inflammatory cell infiltration, and cell death were significantly increased (p < 0.0001). Moreover, deposition of the extracellular matrix and defenestration of sinusoidal fenestrae were observed among 22-month-old mice in the iron overload group. These results suggest that aging is a risk factor for iron-induced liver injury. Therefore, caution should be exercised when performing iron-related treatments in the elderly.
尽管铁是人体中的重要成分，但铁过量会导致铁中毒，影响重要器官。特别是肝脏，因其储存了体内最多的铁，所以受铁中毒的影响相当大。然而，肝脏中铁过载与衰老之间的关系尚未明确。本研究旨在观察衰老对肝脏铁过载的影响。将雌性C57BL/6J小鼠随机分为载体对照组和铁过载组（每组n = 7 - 22只）。铁过载组注射右旋糖酐铁（Fe - dextran，氢氧化铁右旋糖酐复合物）（0.5 g/kg），持续4周。实验期结束后，从2个月、15个月和22个月大的小鼠获取肝脏和血液样本。分析并比较两组之间的肝脏重量、铁沉积、结构变化、细胞死亡、细胞外基质沉积和肝血窦窗孔情况。此外，还进行了生化分析（天冬氨酸转氨酶、丙氨酸转氨酶和血清总铁水平）。与对照组相比，铁过载组随年龄增长呈现出显著差异。在老年铁过载模型中，铁沉积、炎性细胞浸润和细胞死亡显著增加（p < 0.0001）。此外，在铁过载组的22个月大的小鼠中观察到细胞外基质沉积和肝血窦窗孔消失。这些结果表明，衰老可能是铁诱导肝损伤的一个危险因素。因此，在对老年人进行与铁相关的治疗时应谨慎。
