Aflatoxin B1 Exposure in Sheep: Insights into Hepatotoxicity Based on Oxidative Stress, Inflammatory Injury, Apoptosis, and Gut Microbiota Analysis

Yuzhen Sui; Ying Lu; Shoujun Zuo; Haidong Wang; Xiaokun Bian; Guizhen Chen; Shucheng Huang; Hongyu Dai; Fang Liu; Haiju Dong

doi:10.3390/toxins14120840

Aflatoxin B₁ Exposure in Sheep: Insights into Hepatotoxicity Based on Oxidative Stress, Inflammatory Injury, Apoptosis, and Gut Microbiota Analysis

Toxins (Basel). 2022 Dec 1;14(12):840. doi: 10.3390/toxins14120840.

Authors

Affiliation

¹ International Joint Research Center of National Animal Immunology, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China.

Abstract

The widespread fungal toxin Aflatoxin B₁ (AFB₁) is an inevitable pollutant affecting the health of humans, poultry, and livestock. Although studies indicate that AFB₁ is hepatotoxic, there are few studies on AFB₁-induced hepatotoxicity in sheep. Thus, this study examined how AFB₁ affected sheep liver function 24 h after the animals received 1 mg/kg bw of AFB₁ orally (dissolved in 20 mL, 4% v/v ethanol). The acute AFB₁ poisoning caused histopathological injuries to the liver and increased total bilirubin (TBIL) and alkaline phosphatase (AKP) levels. AFB₁ also markedly elevated the levels of the pro-inflammatory cytokines TNF-α and IL-6 while considerably reducing the expression of antioxidation-related genes (SOD-1 and SOD-2) and the anti-inflammatory gene IL-10 in the liver. Additionally, it caused apoptosis by dramatically altering the expression of genes associated with apoptosis including Bax, Caspase-3, and Bcl-2/Bax. Notably, AFB₁ exposure altered the gut microbiota composition, mainly manifested by BF311 spp. and Alistipes spp. abundance, which are associated with liver injury. In conclusion, AFB₁ can cause liver injury and liver dysfunction in sheep via oxidative stress, inflammation, apoptosis, and gut-microbiota disturbance.

Keywords: Aflatoxin B1; apoptosis; gut microbiota; inflammatory; liver function; oxidative stress.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aflatoxin B1 / metabolism
Aflatoxin B1 / toxicity
Animals
Apoptosis
Chemical and Drug Induced Liver Injury* / metabolism
Gastrointestinal Microbiome*
Humans
Liver / metabolism
Oxidative Stress
Sheep
bcl-2-Associated X Protein / metabolism

Substances

Aflatoxin B1
bcl-2-Associated X Protein

Grants and funding

This research was funded by the Henan Province Project for Tackling Key Problems in Science and Technology (92102110079 and 222102110053), the Young Backbone Teachers Project of Colleges and Universities in Henan Province (2018GGJS031), and the National Natural Science Foundation of China (31402187).