Abstract
Aflatoxins have been shown to induce hepatotoxicity in animal models, but the effects of aflatoxin B2 (AFB2) on broiler hepatocytes is unclear. This study aimed to investigate the effects of AFB2 on apoptosis and autophagy to provide an experimental basis for understanding the mechanism of aflatoxin-induced hepatotoxicity. One hundred-twenty Cobb500 broilers were allocated to four groups and exposed to 0 mg/kg, 0.2 mg/kg, 0.4 mg/kg, and 0.8 mg/kg of AFB2 per day for 21 d. AFB2 exerted potent proapoptotic and proautophagic effects on hepatocytes, with increased numbers of apoptotic and autophagic hepatocytes.Poly ADP-ribose polymerase (PARP) was cleaved and caspase-3 was activated in experimental groups, showing that the apoptosis of hepatocytes was triggered by AFB2. Increased levels of the autophagy factors Beclin-1 and LC3-II/LC3-I, as well as down-regulation of p62, a marker of autophagic flux, provided additional evidence for AFB2-triggered autophagy. AFB2 induced mitochondria-mediated apoptosis via the production of reactive oxygen species (ROS) and promotion of the translocation of Bax and cytochrome c (cyt c) between mitochondria and the cytosol, triggering the formation of apoptosomes. AFB2 also inhibited the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway by activating PI3K, Akt, and mTOR and inhibiting their phosphorylation, contributing to the proautophagic activity of AFB2. These findings provide new insights into the mechanisms involved in AFB2-induced hepatotoxicity in broilers.
Highlights
Aflatoxins are known to have strong hepatotoxic and carcinogenic effects and contaminate a wide variety of tropical and subtropical foodstuffs [1]
The results suggested that aflatoxin B2 (AFB2) inhibited hepatocyte growth in broilers by inducing the apoptosis of hepatocytes in a dosedependent manner
The results suggested that AFB2induced autophagy of hepatocytes in broilers occurred via a PI3K/Akt/mTOR-mediated autophagy pathway
Summary
Aflatoxins are known to have strong hepatotoxic and carcinogenic effects and contaminate a wide variety of tropical and subtropical foodstuffs [1]. Aflatoxins are difuranocoumarin compounds, which include B1, B2, G1, G2, M1, and M2. The toxicity of aflatoxin B1 (AFB1) has been shown to be higher that that of other common aflatoxins [2, 3]. Aflatoxins are deleterious to poultry, aflatoxin-contaminated feed is practically unavoidable. Previous studies indicated that low doses of AFB1 produced such responses in poultry and that poultry were extremely sensitive to the toxic effects of AFB1. Research showed that the consumption of AFB1-contaminated feed by poultry had various adverse effects, including liver damage, immunosuppression, and poor growth [6]. The administration of AFB1 to developing chickens caused DNA damage in the liver, morphological defects, and embryonic mortality [7]
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