Cell lines

Tobacco suspension cells

Preparation Method

Tobacco suspension cells were treated with 100 μM fusaric acid and then analyzed for H2O2 accumulation and mitochondrial functions.

Reaction Conditions

100 μM; 240 min

Applications

Cells undergoing fusaric acid-induced programmed cell death exhibited H2O2 production, lipid peroxidation, and a decrease of the catalase and ascorbate peroxidase activities.

Animal models

crossbred barrows

Preparation Method

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.

Dosage form

0 or 200 mg/kg; orally

Applications

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.

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 IC₅₀of 240.8 μg/ml and Thp-1 with IC₅₀of 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]

References:
[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‐ ranslational 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.