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

Toxins (Basel). 2019 Jan 7;11(1):23. doi: 10.3390/toxins11010023.

Abstract

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.

Keywords: Aflatoxin B1; Broilers; Grape Seed Proanthocyanidin Extract; Immunotoxicity; NF-κB; Nrf2; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aflatoxin B1 / toxicity*
  • Animals
  • Antioxidants / pharmacology*
  • Chickens
  • Cytokines / blood
  • Cytokines / genetics
  • Grape Seed Extract / pharmacology*
  • Liver / drug effects
  • Liver / metabolism
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects
  • Proanthocyanidins / pharmacology*
  • Signal Transduction / drug effects
  • Spleen / drug effects
  • Spleen / metabolism

Substances

  • Antioxidants
  • Cytokines
  • Grape Seed Extract
  • Grape Seed Proanthocyanidins
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Proanthocyanidins
  • Aflatoxin B1