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

葡萄籽原花青素提取物通过调节 NF-κB 和 Nrf2 信号通路减轻肉鸡中黄曲霉毒素 B₁ 诱导的免疫毒性和氧化应激

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作者:Shahid Ali Rajput, Lvhui Sun, Ni-Ya Zhang, Mahmoud Mohamed Khalil, Zhao Ling, Li Chong, Shuai Wang, Imran Rashid Rajput, Dost Muhammad Bloch, Farhan Anwar Khan, Aftab Shaukat, Desheng Qi

Abstract

Aflatoxin B&sub1; (AFB&sub1;) 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 AFB&sub1;-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 + AFB&sub1; 1mg/kg contaminated corn (AFB&sub1;); 3. Basal diet + GSPE 250 mg/kg (GSPE); 4. Basal diet + AFB&sub1; 1 mg/kg + GSPE 250 mg/kg (AFB&sub1; + GSPE). The results showed that GSPE significantly decreased serum inflammatory cytokines TNF-α, IFN-γ, IL-1β, IL-10, and IL-6 induced by AFB&sub1;. Similarly, GSPE + AFB&sub1; 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 AFB&sub1; 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 AFB&sub1;. 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 AFB&sub1; group. Taken together, GSPE alleviates AFB&sub1;-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 AFB&sub1;-induced immunotoxicity and oxidative damage.

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