Theaflavins attenuate iron overload-induced liver oxidative injury by inhibiting hepatocyte ferroptosis

作者：Junzhou Chen, Mingdao Mu, Xin Lai, Chen Liu, Yuheng Luo, Jun He, Bing Yu, Quyuan Wang, Huifen Wang, Daiwen Chen, Aimin Wu · 发表于：International Journal of Biological Sciences · 年份：2025 · DOI：10.7150/ijbs.103971 · 被引用次数：15 · 研究领域：Ferroptosis and cancer prognosis、Iron Metabolism and Disorders、Trace Elements in Health

Liver, as a major iron storage organ, is particularly sensitive to oxidative stress-induced damage stemming from iron overload.Thus, antioxidant therapies are often used to reverse oxidative stress-induced tissues damage, however, the cellular mechanisms remain enigmatic.This study investigated the protective effects and mechanisms of theaflavins, a nature production from tea, against oxidative damage in iron overload hepatocytes and mouse liver.Iron overload disrupted iron metabolism in hepatocytes by activating inflammation and enhancing HO-1 expression, leading to hepatic ferroptosis and serious liver damage.Additionally, iron overload inhibited Xc -system (SLC7A11 and SLC3A2), decreasing GSH synthesis, ultimately further induced ferroptosis.Intriguingly, theaflavins supplementation robustly counteracted iron overload-induced ferroptosis and subsequent liver damage.Notably, inhibition of HO-1 and activation of Xc -system provided the mechanistic insights into theaflavins inhibition of hepatocytes ferroptosis.Take together, these results highlight ferroptosis as an inducer of iron overload-induced liver damage, which is inhibited by theaflavins.This nature product form tea represents a potential therapeutic approach to attenuating organ damage in iron overload individuals.