Selenium mitigated aflatoxin B1-induced cardiotoxicity with potential regulation of 4 selenoproteins and ferroptosis signaling in chicks

The aim of the present study was to explore the underlying mechanism of selenium (Se)-mediated detoxification of aflatoxin B1 (AFB1)-induced cardiotoxicity in chicks. A Se-deficient, corn-soybean meal-basal diet (36 mu g Se/ kg, BD) and three test diets (BD+1.0 mg AFB1/kg, 0.3 mg Se/kg, or 1.0 mg AFB1/kg+0.3 mg Se/kg) were used in a 3-wk 2 x 2 factorial design trial (n = 30 chicks/group). Dietary AFB1 led to induced (P <= 0.05) serum creatine kinase and creatine kinase MB isoenzyme activities and heart histopathologic lesions. However, Se deficiency aggravated most of these alterations induced by AFB1. Moreover, mRNA levels of two ferroptosis activators (solute carrier family 11 Member 2 and transferrin) were upregulated (P <= 0.05) in the AFB1-treated groups. Additionally, Se deficiency reduced (P <= 0.05) glutathione peroxidase (GPX) 3 and thioredoxin reductase 3 mRNA and GPX activity but increased (P <= 0.05) selenoprotein M and selenophosphate synthetase 2 mRNA in the heart in AFB1-administered groups. The in vitro study showed that Se alleviated (P <= 0.05) AFB1-reduced cell viability and induced (P <= 0.05) ROS and ferroptosis in H9C2 cardiac cells. It also downregulated (P <= 0.05) two ferroptosis activators (long-chain acyl-CoA synthetase 4 and solute carrier family 11 Member 2) in the AFB1-treated groups in the H9C2 cells. In conclusion, this study illustrated that Se alleviates AFB1-induced cardiotoxicity and cardiomyocyte damage potentially related to the regulation of redox status, 4 selenoproteins, and ferroptosis-related signaling.