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

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.