Spermidine Alleviates Liver Damage Induced by Iron Overload by Inhibiting Oxidative Stress.

Authors

Shuo Li, Yilian Wang, Shiyu Cheng, Yuxuan Qi, Yuxin Qi, Xinyi Wang, Bo Kang

Published in

Biological trace element research. Jul 15, 2026. Epub Jul 15, 2026.

Abstract

Liver diseases are usually accompanied by the occurrence of oxidative stress, and imbalance in hepatic iron homeostasis is a key factor leading to hepatic oxidative stress. Spermidine, as a natural antioxidant, whether it can alleviate the oxidative stress caused by iron homeostasis imbalance remains unclear. This study examined whether spermidine could mitigate iron overload in the liver induced by dextran iron. The results indicate that liver damage caused by iron overload includes disruption of the lobular structure, proliferation of Kupffer cells, and substantial iron deposition (P < 0.001), concurrent with increased MDA and ROS levels (P < 0.001). Furthermore, iron overload markedly upregulated the expression of pro-inflammatory, including TNF-α, IL-1β, IL-6, IFN-γ, CXCL10, and IL-12 (P < 0.001). Meanwhile, iron overload elevated serum TBIL (P < 0.001) but reduced ALT and AST levels (P < 0.05). Spermidine markedly reduces hepatic MDA, ROS, and iron ion levels induced by dextran iron while simultaneously enhancing the hepatic antioxidant capacity. Mechanistically, it suppresses the expression of pro-inflammatory genes such as TNF-α, IL-1β, IL-6, CXCL-10 and IL-12 (P < 0.05), and upregulates key antioxidant proteins, including Nrf2, HO-1, and GPX4, thus alleviating liver injury induced by iron overload. Spermidine is not a direct iron chelator and does not reduce serum iron levels; instead, it indirectly regulates hepatic iron distribution and deposition via oxidative stress suppression. In conclusion, spermidine can alleviate liver toxicity caused by iron overload by reducing oxidative damage to the liver.

PMID:
42458157
Bibliographic data and abstract were imported from PubMed on 16 Jul 2026.

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