Aflatoxin B1 triggers apoptosis in rabbit hepatocytes via mediating oxidative stress and switching on the mitochondrial apoptosis pathway

Lu Zhang; Shaowen Shi; Ying Liu; Yuqing Cui; Yixuan Zhu; Yongzhan Bao; Baojiang Chen; Wanyu Shi

doi:10.1016/j.ecoenv.2023.115478

Aflatoxin B1 triggers apoptosis in rabbit hepatocytes via mediating oxidative stress and switching on the mitochondrial apoptosis pathway

Ecotoxicol Environ Saf. 2023 Oct 1:264:115478. doi: 10.1016/j.ecoenv.2023.115478. Epub 2023 Sep 14.

Authors

Lu Zhang¹, Shaowen Shi¹, Ying Liu¹, Yuqing Cui¹, Yixuan Zhu¹, Yongzhan Bao², Baojiang Chen³, Wanyu Shi⁴

Affiliations

¹ College of Traditional Chinese Veterinary Medicine, Hebei Agricultural University, Baoding 071001, China.
² College of Traditional Chinese Veterinary Medicine, Hebei Agricultural University, Baoding 071001, China; Hebei Provincial Veterinary Biotechnology Innovation Center, Baoding 071001, China.
³ College of Animal Science and Technology, Hebei Agricultural University, Baoding 071001, China.
⁴ College of Traditional Chinese Veterinary Medicine, Hebei Agricultural University, Baoding 071001, China; Hebei Provincial Veterinary Biotechnology Innovation Center, Baoding 071001, China. Electronic address: shiwanyu2010@126.com.

PMID: 37716070
DOI: 10.1016/j.ecoenv.2023.115478

Abstract

Aflatoxin B1 (AFB1) is considered the most toxic carcinogenic compound, and exposure to AFB1 is highly associated with hepatocellular carcinoma. The aim of this study was to investigate the effects of different doses of AFB1 on growth performance and the liver of rabbits, as well as explore its underlying mechanisms. A total of eighty 30-day-old meat rabbits were randomly divided into four treatments. The control group was fed a pollution-free diet, while the AFL, AFM, and AFH groups were fed contaminated diets containing 13 μg/kg, 19 μg/kg, and 25 μg/kg of AFB1, respectively. The results showed that AFB1 had detrimental effects on the production performance of rabbits, resulting in decreased weight gain. Additionally, AFB1 exposure was associated with increased activity of Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT), as well as decreased levels of total protein (TP) and albumin (ALB) in the serum. AFB1 induced the production of reactive oxygen species (ROS) and malondialdehyde (MDA) while inhibiting the activity of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activity in liver tissues. AFB1 decreased the mRNA transcription and protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H dehydrogenase quinone-1 (NQO-1). AFB1 not only decreased the contents of cytochrome P4501A2 (CYP1A2), cytochrome P4502A6 (CYP2A6) and cytochrome P4503A4 (CYP3A4) but also increased the content of AFB1-DNA adducts in the liver. Furthermore, AFB1 enhanced the expression of cytochrome c (cyt-c), caspase-9, caspase-3, and Bcl-2-associated X protein (Bax), while inhibiting the expression of B-cell lymphoma 2 (Bcl-2). Therefore, we demonstrated that AFB1 triggered apoptosis in rabbit hepatocytes via mediating oxidative stress and switching on the mitochondrial apoptosis pathway, and decreased rabbit performance.

Keywords: Aflatoxin B1; Apoptosis; Liver injury; Nrf2 pathway; Oxidative stress.

MeSH terms

Aflatoxin B1* / toxicity
Animals
Antioxidants / metabolism
Apoptosis
Cytochromes
Glutathione / metabolism
Hepatocytes
Liver
Oxidative Stress*
Rabbits

Substances

Aflatoxin B1
Antioxidants
Glutathione
Cytochromes