Selenium Deficiency Aggravates Aflatoxin B1-Induced Immunotoxicity in Chick Spleen by Regulating 6 Selenoprotein Genes and Redox/Inflammation/Apoptotic Signaling

Background: Selenium (Se) plays a protective role in aflatoxin B-1 (AFB(1))-induced splenic immunotoxicity in chicks. Objective: This study was designed to reveal the underlying mechanism of Se-mediated protection against AFB(1)-induced splenic injury in broilers. Methods: Four groups of 1-d-old Cobb male broilers (n = 5 cages/diet, 6 chicks/cage) were arranged in a 3-wk 2 x 2 factorial design trial whereby they were fed an Se-deficient, corn-and soy-based diet [base diet (BD), 36 mu g Se/kg], BD plus 1.0 mg AFB(1)/kg, BD plus 0.3 mg Se/kg, or BD plus 1.0 mg AFB(1)/kg and 0.3 mg Se/kg (as 2-hydroxy-4-methylselenobutanoic acid). Serum and spleen were collected at week 3 to assay for cytokines, histology, redox status, selected inflammation-and apoptosis-related genes and proteins, and the selenogenome. Results: Dietary AFB(1) induced growth retardation and spleen injury, decreasing (P < 0.05) body weight gain, feed intake, feed conversion efficiency, and serum interleukin-1 beta by 17.8-98.1% and increasing (P < 0.05) the spleen index and serum interleukin-6 by 37.6-113%. It also reduced the splenic lymphocyte number, the white pulp region, and histiocyte proliferation in Se-adequate groups. However, Se deficiency aggravated (P < 0.05) these AFB(1)-induced alterations by 16.2-103%. Moreover, Se deficiency decreased (P < 0.05) splenic glutathione peroxidase (GPX) activity and glutathioneS transferase and glutathione concentrations by 35.6-89.4% in AFB(1)-exposed groups. Furthermore, Se deficiency upregulated (P < 0.05) the apoptotic (Caspase 3 and Caspase 9) and antimicrobial (beta defensin 1 and 2) genes, but downregulated (P < 0.05) antiapoptotic (B-cell lymphoma 2) and inflammatory (E3 ubiquitin-protein ligase CBL-B) genes at the mRNA and/or protein level in AFB(1) supplementation groups. Additionally, Se deficiency downregulated (P < 0.05) GPX3, thioredoxin reductase 1 (TXNRD 1), GPX4, and selenoprotein (SELENO) S, and upregulated (P < 0.05) SELENOT and SELENOU in spleen in AFB(1) administered groups. Conclusions: Dietary Se deficiency exacerbated AFB(1)-induced spleen injury in chicks, partially through the regulation of oxidative stress, inflammatory and apoptotic signaling, and 6 selenoproteins.