Grape Seed Proanthocyanidin Extract Alleviates AflatoxinB1-Induced Immunotoxicity and Oxidative Stress via Modulation of NF-κB and Nrf2 Signaling Pathways in Broilers

Aflatoxin B1 (AFB1) is a widely spread mycotoxin contaminates food and feed, causing severe oxidative stress damages and immunotoxicity. Grape seed proanthocyanidin (GSPE), a natural antioxidant with wide range of pharmacological and medicinal properties. The goal of the present study was to investigate the protective effects of GSPE against AFB1-induced immunotoxicity and oxidative stress via NF-&kappa:B and Nrf2 signaling pathways in broiler chickens. For the experiment, 240 one-day old Cobb chicks were allocated into four dietary treatment groups of six replicates (10 birds per replicate): 1. Basal diet (control): 2. Basal diet + AFB1 1mg/kg contaminated corn (AFB1): 3. Basal diet + GSPE 250 mg/kg (GSPE): 4. Basal diet + AFB1 1 mg/kg + GSPE 250 mg/kg (AFB1 + GSPE). The results showed that GSPE significantly decreased serum inflammatory cytokines TNF-&alpha:, IFN-&gamma:, IL-1&beta:, IL-10, and IL-6 induced by AFB1. Similarly, GSPE + AFB1 treated group revealed a significant decrease in mRNA expressions of pro-inflammatory cytokines (TNF-&alpha:, IFN-&gamma:, IL-1&beta:, and IL-6) in the splenic tissue compared to the AFB1 treatment group. In addition, western blotting results manifested that GSPE treatment normalized the phosphorylation of nuclear factor kappa B (p65) and the degradation of I&kappa:B&alpha: protein induced by AFB1. Furthermore, GSPE enhanced the antioxidant defense system through activating the nuclear factor-erythroid-2-related factor (Nrf2) signaling pathway. The mRNA and protein expression level of Nrf2 and its down streaming associated genes were noted up-regulated by the addition of GSPE, and down-regulated in the AFB1 group. Taken together, GSPE alleviates AFB1-induced immunotoxicity and oxidative damage by inhibiting the NF-&kappa:B and activating the Nrf2 signaling pathways in broiler chickens. Conclusively, our results suggest that GSPE could be considered as a potential natural agent for the prevention of AFB1-induced immunotoxicity and oxidative damage.