Sesamin attenuates PM-induced cardiovascular injury by inhibiting ferroptosis in rats.

: This study aimed to elucidate the pharmacological effects of sesamin (Ses) and its mechanism of action towards PM-induced cardiovascular injuries. : Forty Sprague Dawley (SD) rats were randomly divided into five groups: a saline control group; a PM exposure group; and low-, middle-, and high-dose Ses pretreatment groups. The SD rats were pretreated with different concentrations of Ses for 21 days. Afterward, the rats were exposed to ambient PM by intratracheal instillation every other day for a total of three times. The levels of inflammatory markers, including tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and interleukin-6 (IL-6), and indicators related to oxidative responses, such as total superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA), were measured in the blood and heart. The expression of ferroptosis-related proteins in heart tissues was determined western blot and immunohistochemistry. : Ses pretreatment substantially ameliorated cardiovascular injuries in rats as evidenced by the decrease in the pathological score and collagen area. The decreased levels of SOD, GSH, and GSH-Px in the heart and serum were inhibited by Ses. In addition, Ses not only notably increased the activity of antioxidant enzymes but also reduced the levels of MDA, CK, LDH, CK-MB, IL-6, TNF-α, IL-1β, and IL-6. Furthermore, Ses pretreatment upregulated the expression levels of GPX4, SLC7A11, TFRC, and FPN1 and inhibited the expression levels of FTH1 and FTL. : Ses pretreatment could ameliorate PM-induced cardiovascular injuries perhaps by inhibiting ferroptosis. Therefore, Ses pretreatment may be a novel strategy for the prevention and treatment of PM-induced cardiovascular injury.