Background
Fusaric acid, as a mycotoxin produced by the Fusarium species, has diverse toxicological effects in plants and animals.[1]
In vitro, treatment with 104 μg/ml fusaric acid in human hepatocellular carcinoma (HepG2) cells post-translationally activates p53 in response to DNA damage.[2] In vitro efficacy test it shown that in HepG2 cells fusaric acid remarkably increased p53 promoter methylation in the 25, 104, and 150 μg/ml fusaric acid treatments; but in the 50 μg/ml fusaric acid treatment significantly decreased the promoter methylation of p53. [1] In HepG2 cells, fusaric acid dramatically increased promoter methylation of DNMT1 compared to the control; however, treatment with 25, 50, and 104 μg/ml fusaric acid decreased the promoter methylation of DNMT3A and treatment with 150 μg/ml increased the promoter methylation of DNMT3A.[3] Fusaric acid has toxicity (24 h incubation; IC50 = 104 μg/ml) on mitochondrial output, cellular and mitochondrial stress responses, mitochondrial biogenesis and markers of cell death.[4] In addition, fusaric acid has cytotoxicity to PBMCs with IC50 of 240.8?μg/ml and Thp-1 with IC50 of 107.7?μg/ml cells at 24?h.[5]
In vivo experiment it indicated that treatment with 100 mg/kg body weight fusaric acid intraperitoneally 30 min prior to the onset of the dark phase (lights out) in rats increased the level of brain serotonin (5HT), 5-hydroxyindoleacetic acid (5HIAA), tyrosine (TYRO), and dopamine (DA) and decreased the level of norepinephrine (NEpi).[6]
参考文献:
[1]Ghazi T, et al. Fusaric acid decreases p53 expression by altering promoter methylation and m6A RNA methylation in human hepatocellular carcinoma (HepG2) cells. Epigenetics. 2021 Jan;16(1):79-91.
[2]Ghazi T, Nagiah S, Tiloke C, et al. Fusaric acid induces DNA damage and post‐translational modifications of p53 in human hepatocellular carcinoma (HepG2) cells. J Cell Biochem. 2017. November;118(11):3866–3874.
[3]Ghazi T, et al. Fusaric acid-induced promoter methylation of DNA methyltransferases triggers DNA hypomethylation in human hepatocellular carcinoma (HepG2) cells. Epigenetics. 2019 Aug;14(8):804-817.?
[4]Sheik Abdul N, et al. Fusaric acid induces mitochondrial stress in human hepatocellular carcinoma (HepG2) cells. Toxicon. 2016 Sep 1;119:336-44.?
[5]Dhani S, et al. Fusaric Acid immunotoxicity and MAPK activation in normal peripheral blood mononuclear cells and Thp-1 cells. Sci Rep. 2017 Jun 8;7(1):3051.
[6]Porter JK, et al. Fusaric acid in Fusarium moniliforme cultures, corn, and feeds toxic to livestock and the neurochemical effects in the brain and pineal gland of rats. Nat Toxins. 1995;3(2):91-100.
镰刀菌酸是一种由镰刀菌产生的真菌毒素，对动植物具有多种毒理作用。[1]
在体外，用 104 μg/ml 镰刀菌酸处理人肝细胞癌 (HepG2) 细胞后翻译后激活 p53 以响应 DNA 损伤。[2] 体外功效测试表明在 HepG2 细胞中，镰刀菌酸在 25、104 和 150 μg/ml 镰刀菌酸处理中显着增加 p53 启动子甲基化；但在 50 μg/ml 镰刀菌酸处理中显着降低了 p53 的启动子甲基化。 [1] 在 HepG2 细胞中，与对照相比，镰刀菌酸显着增加了 DNMT1 的启动子甲基化；然而，用 25、50 和 104 μg/ml 的镰刀菌酸处理降低了 DNMT3A 的启动子甲基化，用 150 μg/ml 的处理增加了 DNMT3A 的启动子甲基化。[3] 镰刀菌酸具有毒性（孵育 24 小时；IC50 = 104 μg/ml) 对线粒体输出、细胞和线粒体应激反应、线粒体生物合成和细胞死亡标志物的影响。[4] 此外，镰刀菌酸对 PBMCs 具有细胞毒性，IC50 为 240.8μg/ml，Thp-1 的 IC50 为 107.7μg/ml 细胞，在 24>h。[5 ]
体内实验表明，在大鼠黑暗阶段（熄灯）开始前 30 分钟腹腔注射 100 mg/kg 镰刀菌酸可增加脑血清素 (5HT)、5-羟基吲哚乙酸的水平(5HIAA)、酪氨酸 (TYRO) 和多巴胺 (DA)，并降低去甲肾上腺素 (NEpi) 的水平。[6]
Protocol
| Cell experiment [1]: |
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Cell lines
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Tobacco suspension cells
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Preparation Method
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Tobacco suspension cells were treated with 100 μM fusaric acid and then analyzed for H2O2 accumulation and mitochondrial functions.
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Reaction Conditions
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100 μM; 240 min
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Applications
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Cells undergoing fusaric acid-induced programmed cell death exhibited H2O2 production, lipid peroxidation, and a decrease of the catalase and ascorbate peroxidase activities.
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| Animal experiment [2]: |
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Animal models
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crossbred barrows
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Preparation Method
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A total of 40 crossbred barrows (initial weight 10 kg) were orally dosed with 0 or 200 mg of fusaric acid/kg of BW and five animals from each treatment were killed 4.5, 9, 18, or 36 h after dosing. Animals in the group killed 36 h after dosing were observed for behavioral changes.
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Dosage form
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0 or 200 mg/kg; orally
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Applications
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Vomiting was noted in 60% of the pigs dosed with fusaric acid.The major neurochemical changes due to exposure to fusaric acid were seen in the hypothalamus 18 h after dosing.Brain tryptophan, serotonin, and 5-hydroxyindoleacetic acid all tended to be elevated by the action of fusaric acid.
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参考文献:
[1]. Jiao J, et al. Hydrogen peroxide production and mitochondrial dysfunction contribute to the fusaric acid-induced programmed cell death in tobacco cells. J Plant Physiol. 2014 Aug 15;171(13):1197-203.?
[2]. Smith TK, et al. Effect of fusaric acid on brain regional neurochemistry and vomiting behavior in swine. J Anim Sci. 1991 May;69(5):2044-9.
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