Aflatoxin B1 interferes with embryonic liver development: Involvement of p53 signaling and apoptosis in zebrafish

Cheng, Ya-Chih; Wu, Tzu‐Chin; Huang, Ying-Tzu; Chang, Yung Hsien; Yang, Jiann‐Jou; Yu, Feng‐Yih; Liu, Biing-Hui

doi:10.1016/j.tox.2021.152844

Cited by 25 publications

(14 citation statements)

References 58 publications

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“…In accordance with previously conducted studies [ 29 , 31 ] where AFB1 was shown to be teratogenic, increasing the incidence of malformations such as spinal lordosis, pericardial edemas, narrowed head, elongated heart among others, in the present study, we observed that AFB1 exposure strongly affected the development of the embryos. The toxic action of AFB1 is often associated with increased oxidative stress [ 10 , 33 , 34 , 35 , 36 ].…”

Section: Discussionsupporting

confidence: 93%

“…In this study, we used aflatoxin concentrations close to those found in feed and that are known to be toxic based on studies that were previously performed during the early stages of embryonic development in zebrafish larvae [ 10 , 26 ]. Several studies have shown how aflatoxin can cause increased oxidative stress when ingested in excessive amounts and repeatedly in fish models [ 27 , 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…Early developmental exposure of zebrafish larvae to AFB1 may result in developmental alterations such as curvature of the body axis or edema formation in the yolk sac or pericardium. Previous studies have shown that exposure to AFB1 alone or in combination with other mycotoxins in zebrafish embryos can cause toxicity in zebrafish embryos [ 30 , 31 ] as well as behavioral alterations in terms of average velocity and the movement ratio, and can also create neurotoxicity and increase liver size; however, no significant malformations have been shown [ 29 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Aflatoxin B1 Toxicity in Zebrafish Larva (Danio rerio): Protective Role of Hericium erinaceus

Paola

Iaria

Capparucci

et al. 2021

Toxins

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Aflatoxin B1 (AFB1), a secondary metabolite produced by fungi of the genus Aspergillus, has been found among various foods as well as in fish feed. However, the effects of AFB1 on fish development and its associated toxic mechanism are still unclear. In the present study, we confirmed the morphological alterations in zebrafish embryos and larvae after exposure to different AFB1 doses as well as the oxidative stress pathway that is involved. Furthermore, we evaluated the potentially protective effect of Hericium erinaceus extract, one of the most characterized fungal extracts, with a focus on the nervous system. Treating the embryos 6 h post fertilization (hpf) with AFB1 at 50 and 100 ng/mL significantly increased oxidative stress and induced malformations in six-day post-fertilization (dpf) zebrafish larvae. The evaluation of lethal and developmental endpoints such as hatching, edema, malformations, abnormal heart rate, and survival rate were evaluated after 96 h of exposure. Hericium inhibited the morphological alterations of the larvae as well as the increase in oxidative stress and lipid peroxidation. In conclusion: our study suggests that a natural extract such as Hericium may play a partial role in promoting antioxidant defense systems and may contrast lipid peroxidation in fish development by counteracting the AFB1 toxicity mechanism.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Aflatoxin B1 Toxicity in Zebrafish Larva (Danio rerio): Protective Role of Hericium erinaceus

Paola

Iaria

Capparucci

et al. 2021

Toxins

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“…The deleterious effects of AFB1 are not restricted to birds and mammals, and it is possible to observe neurological changes in zebrafish when exposed to this mycotoxin at a dose of 15–75 ng/mL 6 h after fertilization, with marked behavioral change [ 42 ]. Additionally, in zebrafish embryos there are failures in the embryonic development of the liver due to marked apoptosis, in addition to immunological deficiencies [ 43 ]. In general, aflatoxin similarly impacts morpho development during the prenatal period, in addition to impacting mainly the liver of several animal species.…”

Section: Effects Of Prenatal Exposure To Aflatoxin B1 In Animalsmentioning

confidence: 99%

Effects of Prenatal Exposure to Aflatoxin B1: A Review

2021

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Aflatoxins are mycotoxins produced as secondary fungal metabolites. Among them, aflatoxin B1 (AFB1) stands out due to its genotoxic and mutagenic potential, being a potent initiator of carcinogenesis. In this review, the outcomes from the published literature in the past 10 years on the effects of AFB1 pathophysiological mechanisms on embryological and fetal development are discussed. In several animal species, including humans, AFB1 has a teratogenic effect, resulting in bone malformations, visceral anomalies, lesions in several organs, and behavioral and reproductive changes, in addition to low birth weight. The mutagenic capacity of AFB1 in prenatal life is greater than in adults, indicating that when exposure occurs in the womb, the risk of the development of neoplasms is higher. Studies conducted in humans indicate that the exposure to this mycotoxin during pregnancy is associated with low birth weight, decreased head circumference, and DNA hypermethylation. However, as the actual impacts on humans are still unclear, the importance of this issue cannot be overemphasized and studies on the matter are essential.

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“…Zebrafish liver morphogenesis started at 22 hpf and ended at 96 hpf, which can be distinguished by morphological changes and the expression patterns of molecular markers, such as hhex , proxl , foxa3 , and gata6 [ 28 ]. The mesodermal signals, such as Fgf, Bmp, and Wnt signaling are closely involved in the control of hepatoblast specification, which can be marked by prox 1 and hhex at 22 hpf in zebrafish [ 29 , 30 ]. The differentiation and maturation of hepatocytes and outgrowth of zebrafish liver occur between 50 and 96 hpf, which are marked by vitamin D binding protein ( gc ), fatty acid binding protein 10a ( fabp10a ), ceruloplasmin ( cp ), and the dramatic increase in liver size to establish the liver functions [ 31 , 32 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

Comparative Transcriptome Analysis Provides Novel Molecular Events for the Differentiation and Maturation of Hepatocytes during the Liver Development of Zebrafish

Zhao

Song

et al. 2022

Biomedicines

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The liver plays an essential role in multiple biological functions including metabolism, detoxification, digestion, coagulation, and homeostasis in vertebrates. The specification and differentiation of embryonic hepatoblasts, the proliferation of hepatocytes, and the hepatic tissue architecture are well documented, but molecular events governing the maturation of hepatocytes during liver development remain largely unclear. In this study, we performed a comparative transcriptome analysis of hepatocytes that were sorted by flow cytometry from developing zebrafish embryos at 60, 72, and 96 hpf. We identified 667 up-regulated and 3640 down-regulated genes in hepatocytes between 60 and 72 hpf, 606 up-regulated and 3924 down-regulated genes between 60 and 96 hpf, and 1693 up-regulated genes and 1508 down-regulated genes between 72 and 96 hpf. GO enrichment analysis revealed that key biological processes, cellular components, and molecular functions in hepatocytes between 60 to 72 hpf, such as cell cycle, DNA replication, DNA repair, RNA processing, and transcription regulation, are mainly associated with the proliferation of hepatocytes. In addition to biological processes, cellular components, and molecular functions for cell proliferation, molecular functions for carbohydrate metabolism were enriched in hepatocytes during 72 to 96 hpf. KEGG enrichment analysis identified key signaling pathways, such as cell cycle, RNA degradation, ubiquitin-mediated proteolysis, ErbB and Hedgehog signaling, basal transcription factors, Wnt signaling, and glycan degradation, which are closely associated with cell proliferation or carbohydrate metabolism in hepatocytes between 60 to 72 hpf. Newly enriched signaling pathways in hepatocytes during 72 to 96 hpf include metabolisms of pyrimidine, purine, nicotinate and nicotinamide, caffeine, glycine, serine and threonine, ABC transporters, and p53 signaling that function in metabolisms of lipid, protein and energy, cellular secretion, or detoxification, indicating the functional maturation of hepatocytes between 72 to 96 hpf. These findings provide novel clues for further understanding the functional differentiation and maturation of hepatocytes during liver development.

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Aflatoxin B1 interferes with embryonic liver development: Involvement of p53 signaling and apoptosis in zebrafish

Cited by 25 publications

References 58 publications

Aflatoxin B1 Toxicity in Zebrafish Larva (Danio rerio): Protective Role of Hericium erinaceus

Aflatoxin B1 Toxicity in Zebrafish Larva (Danio rerio): Protective Role of Hericium erinaceus

Effects of Prenatal Exposure to Aflatoxin B1: A Review

Comparative Transcriptome Analysis Provides Novel Molecular Events for the Differentiation and Maturation of Hepatocytes during the Liver Development of Zebrafish

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