Abstract
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.