Multi-Fusarium mycotoxin exposure activates Nrf2 and Ahr pathway in the liver of laying hens

Toxicol Lett. 2024 Jan:391:55-61. doi: 10.1016/j.toxlet.2023.12.006. Epub 2023 Dec 12.

Abstract

This study investigates gene expression changes in laying hens exposed to trichothecene mycotoxins, known to induce oxidative stress and affect xenobiotic transformation and antioxidants. A 3-day feeding trial tested low and high doses of T-2/HT-2 toxin, DON/3-AcDON/15-AcDON, and FB1 in hen feed. Results showed increased expression of AHR, AHRR, HSP90, and CYP1A2 genes on days 2 and 3, suggesting a response to mycotoxin exposure. High doses down-regulated CYP1A2, AHR, and AHRR on day 1. KEAP1 expression decreased on day 1 but increased dose-dependently on days 2 and 3. NRF2 was up-regulated by low and down-regulated by high doses on day 1, then increased on days 2 and 3. Antioxidant-related genes (GPX3, GPX4, GSS, GSR) showed dose-dependent responses. Low doses up-regulated GPX3 and GPX4 throughout, while high doses up-regulated GPX3 on days 2 and 3 and GPX4 on day 3. GSS was up-regulated on day 3. Results indicate that toxic metabolites formed by phase I biotransformation rapidly induce ROS formation at low doses through the AHR/Hsp90/CYP1A2 pathway at the gene expression level, but at high levels, ROS-induced oxidative stress manifests later. Study showed simultaneous activation of redox-sensitive pathways: aryl hydrocarbon receptor (Ahr) and nuclear factor erythroid-derived 2-like 2 (Nrf2) by multi-mycotoxin exposure.

Keywords: Aryl hydrocarbon receptor; Deoxynivalenol; Fumonisin B1; Glutathione redox system; Laying hens; Oxidative stress; T2 toxin.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Chickens
  • Cytochrome P-450 CYP1A2 / metabolism
  • Female
  • Fusarium* / metabolism
  • Kelch-Like ECH-Associated Protein 1
  • Liver / metabolism
  • Mycotoxins* / toxicity
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Reactive Oxygen Species / metabolism
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism
  • T-2 Toxin* / metabolism
  • T-2 Toxin* / toxicity

Substances

  • Mycotoxins
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • Cytochrome P-450 CYP1A2
  • Reactive Oxygen Species
  • Receptors, Aryl Hydrocarbon
  • Antioxidants
  • T-2 Toxin