Dietary Se deficiency dysregulates metabolic and cell death signaling in aggravating the AFB1 hepatotoxicity of chicks.

The objective of this study was to use isobaric tags for relative and absolute quantitation (iTRAQ) proteomic technology to systematically analyze the hepatotoxic mechanism of aflatoxin B1 (AFB1) and its prevention by Se in broilers. Four groups of day-old broilers were allocated into a 2 × 2 factorial design trial that fed a Se-deficient based diet (BD) or the BD + 1.0 mg AFB1/kg, 0.3 mg Se/kg, or 1.0 mg AFB1/kg plus 0.3 mg Se/kg for 3 wk. Dietary AFB1 increased serum ALT and decreased total protein and albumin concentrations, and induced hepatic histopathological lesions in Se adequate groups. Notably, Se deficiency exacerbated these AFB1-induced changes. Furthermore, Se deficiency reduced hepatic glutathione peroxidase but increased thioredoxin reductase and glutathione S-transferase activities and 8-hydroxydeoxyguanosine concentration in AFB1 administrated groups. Moreover, AFB1 dysregulated 261 co-differentially expressed proteins (DEPs) in both Se adequate and deficiency diets, and Se deficiency dysregulated 64 DEPs in AFB1 administrated diets. These DEPs are mainly related to phase I and II metabolizing enzymes, heat shock proteins, DNA repair, fatty acid metabolism and apoptosis. The in vitro study has verified that aldo-keto reductase family1, member10 plays an important role in AFB1-induced hepatotoxicity and Se-mediated detoxification of AFB1 in a chicken leghorn male hepatoma cells. Conclusively, this study has analyzed the hepatic proteome response to dietary AFB1 and Se, and thus shed new light on the mechanisms of hepatotoxicity of AFB1 and its detoxification by Se in broilers.