Molecular mechanisms of aflatoxin neurotoxicity and potential neuroprotective agents
Aflatoxins (AFTs) represent one of the most notorious classes of deadly mycotoxins produced by certain fungi that are found on agricultural crops. Aflatoxins are highly toxic to mammals and are known to cause a series of detrimental effects, including neuro-, hepato-, nephron-, and immuno-toxicity....
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| Format: | Article |
| Language: | English |
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Tsinghua University Press
2024-09-01
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| Series: | Food Science and Human Wellness |
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| Online Access: | https://www.sciopen.com/article/10.26599/FSHW.2022.9250201 |
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| author | Chongshan Dai Erjie Tian Hui Li Subhajit Das Gupta Zhihui Hao Zhanhui Wang Tony Velkov Jianzhong Shen |
| author_facet | Chongshan Dai Erjie Tian Hui Li Subhajit Das Gupta Zhihui Hao Zhanhui Wang Tony Velkov Jianzhong Shen |
| author_sort | Chongshan Dai |
| collection | DOAJ |
| description | Aflatoxins (AFTs) represent one of the most notorious classes of deadly mycotoxins produced by certain fungi that are found on agricultural crops. Aflatoxins are highly toxic to mammals and are known to cause a series of detrimental effects, including neuro-, hepato-, nephron-, and immuno-toxicity. In this original review we summarize the mechanisms of aflatoxin-induced neurotoxicity and the clinical potential of novel neuroprotective agents. Aflatoxin B1 (AFB1) is the most toxic congener among the 21 identified AFTs. Recent studies have shown that food borne exposure to AFB1 and/or its metabolites often leads to fatal neurotoxicity in animals and humans. Animal studies indicated that AFB1 exposure could induce abnormal behavioral changes, including anxiety, lethargy disorders, depression-like behavior, cognitive, learning and memory defects, and decreased feeding behavior. Mechanistically, AFB1 exposure has been associated with lipid peroxidation, ablation of non-enzymatic and enzymatic antioxidant defense systems and decreased neurotransmitter levels. AFB1 exposure has also been shown to induce DNA damage, apoptosis, pyroptosis, and mitochondrial dysfunction in the brain tissue. Several signaling pathways, including gasdermin D, toll like receptor 2 (TLR2), TLR4, Akt, NF-κB, ERK/MAPK, protein kinase C (PKC), and mitochondrial apoptotic pathways have been shown to participate in AFB1-induced neuronal or astrocyte cell death. Targeting these pathways by small molecules (e.g., quercetin, curcumin, and gallic acid, and dimethyl fumarate), Chinese herbal extracts (e.g., Artichoke leaf extract, Chelidonium majus ethanolic extract, pumpkin extract, and Crocus sativus L. tea), and probiotic supplements could effectively improve AFB1-induced neurobehavioral abnormalities and neurotoxicity. To date, the precise molecular mechanisms of AFB1-induced neurotoxicity and potential neuroprotective agents remain unclear. In the present review, the clinical manifestations, molecular mechanisms, and potential neuroprotective agents of AFB1-induced neurotoxicity are summarized in the broadest overview. It is most hopeful that this broad reaching review provides valuable insights and stimulates broader discussion to develop the effective neuroprotective agents against aflatoxins. |
| format | Article |
| id | doaj-art-4fff5c76f9eb4d4cbd0e49e562a473da |
| institution | Kabale University |
| issn | 2097-0765 2213-4530 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Tsinghua University Press |
| record_format | Article |
| series | Food Science and Human Wellness |
| spelling | doaj-art-4fff5c76f9eb4d4cbd0e49e562a473da2025-01-10T06:56:56ZengTsinghua University PressFood Science and Human Wellness2097-07652213-45302024-09-011352445245510.26599/FSHW.2022.9250201Molecular mechanisms of aflatoxin neurotoxicity and potential neuroprotective agentsChongshan Dai0Erjie Tian1Hui Li2Subhajit Das Gupta3Zhihui Hao4Zhanhui Wang5Tony Velkov6Jianzhong Shen7National Key Laboratory of Veterinary Public Health and Safety, Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaCollege of Animal Science and Technology, Henan University of Science and Technology, Luoyang 471023, ChinaBeijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Prevention and Control, Beijing 100013, ChinaDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75230, USANational Key Laboratory of Veterinary Public Health and Safety, Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaNational Key Laboratory of Veterinary Public Health and Safety, Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaMonash Biomedicine Discovery Institute, Department of Pharmacology, Monash University, Victoria 3800, AustraliaNational Key Laboratory of Veterinary Public Health and Safety, Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaAflatoxins (AFTs) represent one of the most notorious classes of deadly mycotoxins produced by certain fungi that are found on agricultural crops. Aflatoxins are highly toxic to mammals and are known to cause a series of detrimental effects, including neuro-, hepato-, nephron-, and immuno-toxicity. In this original review we summarize the mechanisms of aflatoxin-induced neurotoxicity and the clinical potential of novel neuroprotective agents. Aflatoxin B1 (AFB1) is the most toxic congener among the 21 identified AFTs. Recent studies have shown that food borne exposure to AFB1 and/or its metabolites often leads to fatal neurotoxicity in animals and humans. Animal studies indicated that AFB1 exposure could induce abnormal behavioral changes, including anxiety, lethargy disorders, depression-like behavior, cognitive, learning and memory defects, and decreased feeding behavior. Mechanistically, AFB1 exposure has been associated with lipid peroxidation, ablation of non-enzymatic and enzymatic antioxidant defense systems and decreased neurotransmitter levels. AFB1 exposure has also been shown to induce DNA damage, apoptosis, pyroptosis, and mitochondrial dysfunction in the brain tissue. Several signaling pathways, including gasdermin D, toll like receptor 2 (TLR2), TLR4, Akt, NF-κB, ERK/MAPK, protein kinase C (PKC), and mitochondrial apoptotic pathways have been shown to participate in AFB1-induced neuronal or astrocyte cell death. Targeting these pathways by small molecules (e.g., quercetin, curcumin, and gallic acid, and dimethyl fumarate), Chinese herbal extracts (e.g., Artichoke leaf extract, Chelidonium majus ethanolic extract, pumpkin extract, and Crocus sativus L. tea), and probiotic supplements could effectively improve AFB1-induced neurobehavioral abnormalities and neurotoxicity. To date, the precise molecular mechanisms of AFB1-induced neurotoxicity and potential neuroprotective agents remain unclear. In the present review, the clinical manifestations, molecular mechanisms, and potential neuroprotective agents of AFB1-induced neurotoxicity are summarized in the broadest overview. It is most hopeful that this broad reaching review provides valuable insights and stimulates broader discussion to develop the effective neuroprotective agents against aflatoxins.https://www.sciopen.com/article/10.26599/FSHW.2022.9250201aflatoxin b1 (afb1)neurotoxicitymolecular mechanismschemical preventions |
| spellingShingle | Chongshan Dai Erjie Tian Hui Li Subhajit Das Gupta Zhihui Hao Zhanhui Wang Tony Velkov Jianzhong Shen Molecular mechanisms of aflatoxin neurotoxicity and potential neuroprotective agents Food Science and Human Wellness aflatoxin b1 (afb1) neurotoxicity molecular mechanisms chemical preventions |
| title | Molecular mechanisms of aflatoxin neurotoxicity and potential neuroprotective agents |
| title_full | Molecular mechanisms of aflatoxin neurotoxicity and potential neuroprotective agents |
| title_fullStr | Molecular mechanisms of aflatoxin neurotoxicity and potential neuroprotective agents |
| title_full_unstemmed | Molecular mechanisms of aflatoxin neurotoxicity and potential neuroprotective agents |
| title_short | Molecular mechanisms of aflatoxin neurotoxicity and potential neuroprotective agents |
| title_sort | molecular mechanisms of aflatoxin neurotoxicity and potential neuroprotective agents |
| topic | aflatoxin b1 (afb1) neurotoxicity molecular mechanisms chemical preventions |
| url | https://www.sciopen.com/article/10.26599/FSHW.2022.9250201 |
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