Quercetin ameliorates ochratoxin A-Induced immunotoxicity in broiler chickens by modulation of PI3K/AKT pathway

Chem Biol Interact. 2022 Jan 5:351:109720. doi: 10.1016/j.cbi.2021.109720. Epub 2021 Oct 28.

Abstract

Ochratoxin A (OTA) is a fungal secondary metabolite produced by certain species of Aspergillus and Penicillium, and exerts immunosuppressive effect on humans and animals. Quercetin (QUE) is one of the flavonoids produced as a plant-secondary metabolite. The present study was designed to evaluate the efficacy of QUE against the immunotoxic hazard of OTA in broiler chickens. Forty one-day-old broiler chicks were randomly and equally allocated into four groups; control, OTA (0.5 mg/kg feed), QUE (0.5 g/kg feed) and OTA + QUE (0.5 mg/kg OTA + 0.5 g/kg QUE). The results revealed that dietary OTA induced a significant decrease in the antibody response to Newcastle Disease (ND), Infectious Bronchitis (IB) and Avian Influenza (AI) vaccination and in the lymphoproliferative response to Phytohemagglutinin-P (PHA-P). Ochratoxin A also induced oxidative stress and lipid peroxidation in the bursa of Fabricius, spleen and thymus tissues of chickens as demonstrated by decreased CAT and GSH levels and increased TBARS content. In addition, administration of OTA resulted in apoptosis, which was evident by the increased expression level of PTEN, Bax and Caspase-3 genes and decreased expression level of PI3K, AKT and Bcl-2 genes. Furthermore, exposure to OTA resulted in various pathological lesions in the bursa of Fabricius, spleen and thymus of chickens. On the other hand, administration of QUE ameliorated most of the immunotoxic effects of OTAby its immunomodulatory, antioxidant and anti-apoptotic activities. Taken together, the results suggested that QUE potentially alleviated the OTA-induced immunotoxicity in broiler chickens, probably through amelioration of oxidative stress and activation of the PI3K/AKT signaling pathway.

Keywords: Apoptosis; Bursa of fabricius; Immunomodulation; Oxidative stress; Spleen; Thymus.

MeSH terms

  • Animals
  • Antibody Formation / drug effects
  • Antioxidants / therapeutic use*
  • Avian Proteins / metabolism
  • Bursa, Synovial / drug effects
  • Bursa, Synovial / pathology
  • Chickens
  • Gene Expression / drug effects
  • Immunologic Factors / therapeutic use*
  • Ochratoxins / toxicity*
  • Oxidative Stress / drug effects
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Quercetin / therapeutic use*
  • Signal Transduction / drug effects*
  • Spleen / drug effects
  • Spleen / pathology
  • Thymus Gland / drug effects
  • Thymus Gland / pathology

Substances

  • Antioxidants
  • Avian Proteins
  • Immunologic Factors
  • Ochratoxins
  • ochratoxin A
  • Quercetin
  • Proto-Oncogene Proteins c-akt