Effects of Aging on the Severity of Liver Injury in Mice With Iron Overload

Abstract

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.