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

• Published in: Toxins 2019-01, Vol.11 (1), p.23
• Main Authors: Rajput, Shahid Ali, Sun, Lvhui, Zhang, Ni-Ya, Khalil, Mahmoud Mohamed, Ling, Zhao, Chong, Li, Wang, Shuai, Rajput, Imran Rashid, Bloch, Dost Muhammad, Khan, Farhan Anwar, Shaukat, Aftab, Qi, Desheng
• Format: Article
• Language: English
• Subjects: Aflatoxin B1; Aflatoxin B1 - toxicity; Aflatoxins; Animals; Antioxidants; Antioxidants - pharmacology; Broilers; Chickens; Cytokines; Cytokines - blood; Cytokines - genetics; Damage; Diet; Food contamination; Gene expression; Grape Seed Extract - pharmacology; Grape Seed Proanthocyanidin Extract; Grapes; IL-1β; Immune system; Immunotoxicity; Inflammation; Interleukin 10; Interleukin 6; Liver; Liver - drug effects; Liver - metabolism; mRNA; Mycotoxins; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; NF-kappa B - metabolism; NF-κB; NF-κB protein; Nrf2; Oxidative stress; Oxidative Stress - drug effects; Phosphorylation; Poultry; Proanthocyanidins; Proanthocyanidins - pharmacology; Protein expression; Proteins; Seeds; Signal transduction; Signal Transduction - drug effects; Signaling; Spleen; Spleen - drug effects; Spleen - metabolism; Streaming; Toxicity; Tumor necrosis factor-α; Western blotting; γ-Interferon
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins11010023

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-κB 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-α, IFN-γ, IL-1β, 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-α, IFN-γ, IL-1β, 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 IκBα 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-κB 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.