Fusaric Acid, a picolinic acid derivative isolated from Fusarium heterosporium, is a fungal phytotoxin[1]. Fusaric Acid induces chloroplast and mitochondrial dysfunction, lipid peroxidation, protein damage and DNA fragmentation, causing wilting, necrotic spots on leaves, and reduction in root and root hair growth[2]. Fusaric Acid has been widely used in plant toxicity research to induce oxidative stress damage models in plant cells[3].
In vitro, Fusaric Acid treatment for 24 hours significantly inhibited the viability of human peripheral blood mononuclear cells (PBMCs) and Thp-1 cells, with IC50 values of 240.8μg/ml and 107.7μg/ml, respectively[4]. 200µg/ml Fusaric Acid incubation for 24 hours promoted cell death in HepG2 cells, decreased intracellular ATP levels, and downregulated the expression of mitochondrial stress response proteins SIRT3 and LON[5]. Incubation with 200µg/ml Fusaric Acid for 24 hours induced apoptosis in SNO cells, accompanied by increased Bax expression and decreased Bcl-2 expression[6].
In vivo, Fusaric acid treatment via oral administration at a dose of 100mg/kg/day for 14 days inhibited isoproterenol-induced cardiac hypertrophy and dysfunction, and alleviated cardiac fibrosis in mice[7]. Oral administration of Fusaric acid at a dose of 50mg/kg daily for 10 days reduced ATP levels, decreased the Akt signaling pathway, and increased the expression of glucose receptors in the brain tissues of mice[8].
References:
[1] López‐Díaz C, Rahjoo V, Sulyok M, et al. Fusaric acid contributes to virulence of Fusarium oxysporum on plant and mammalian hosts[J]. Molecular Plant Pathology, 2018, 19(2): 440-453.
[2] Iqbal N, Czékus Z, Ördög A, et al. Fusaric acid-evoked oxidative stress affects plant defence system by inducing biochemical changes at subcellular level[J]. Plant Cell Reports, 2024, 43(1): 2.
[3] Singh V K, Upadhyay R S. Fusaric acid induced cell death and changes in oxidative metabolism of Solanum lycopersicum L[J]. Botanical studies, 2014, 55(1): 66.
[4] Dhani S, Nagiah S, Naidoo D B, et al. Fusaric Acid immunotoxicity and MAPK activation in normal peripheral blood mononuclear cells and Thp-1 cells[J]. Scientific reports, 2017, 7(1): 3051.
[5] Abdul N S, Nagiah S, Chuturgoon A A. Fusaric acid induces mitochondrial stress in human hepatocellular carcinoma (HepG2) cells[J]. Toxicon, 2016, 119: 336-344.
[6] Devnarain N, Tiloke C, Nagiah S, et al. Fusaric acid induces oxidative stress and apoptosis in human cancerous oesophageal SNO cells[J]. Toxicon, 2017, 126: 4-11.
[7] Li X, Zhang Z L, Wang H F. Fusaric acid (FA) protects heart failure induced by isoproterenol (ISP) in mice through fibrosis prevention via TGF-β1/SMADs and PI3K/AKT signaling pathways[J]. Biomedicine & Pharmacotherapy, 2017, 93: 130-145.
[8] Dhani S, Ghazi T, Nagiah S, et al. Fusaric acid alters Akt and ampk signalling in c57bl/6 mice brain tissue[J]. Food and Chemical Toxicology, 2020, 138: 111252.