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

Abstract

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 μg 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 × 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.

Keywords: Aflatoxin B(1); Chicks; Ferroptosis; Heart; Selenium; Selenoproteins.