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

• Published in: Ecotoxicology and environmental safety 2023-10, Vol.264, p.115478-115478, Article 115478
• Main Authors: Zhang, Lu, Shi, Shaowen, Liu, Ying, Cui, Yuqing, Zhu, Yixuan, Bao, Yongzhan, Chen, Baojiang, Shi, Wanyu
• Format: Article
• Language: English
• Subjects: Aflatoxin B1; Apoptosis; Liver injury; Nrf2 pathway; Oxidative stress
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2023.115478

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. [Display omitted] •AFB1 reduces the growth performance of meat rabbits.•AFB1 promotes oxidative stress and evokes apoptosis in rabbit liver.•AFB1 induces oxidative stress by inhibiting Nrf2/HO-1 pathway.•AFB1 induces apoptosis by trigging the mitochondrial apoptosis pathway.