Fumonisin B2 is a selective ceramide synthase inhibitor and carcinogenic mycotoxin [1]. Fumonisin B2 can induce an increase in the mRNA expression of the p21 gene and a decrease in the mRNA expression of the cyclin D1 gene, thereby altering the cell cycle progression[2]. Fumonisin B2 has been widely used to induce cytotoxicity and DNA fragmentation in turkey peripheral blood lymphocytes [3].
In vitro, Fumonisin B2 treatment for 96 hours significantly inhibited the viability of H4TG, FaO, and MDCK cells, with IC50 values of 2, 5, and 2µg/ml, respectively[4]. Treatment with 40µM Fumonisin B2 for 48 hours significantly inhibited the proliferation of GES-1 cells, increased the level of lactate dehydrogenase, and induced endoplasmic reticulum stress[5]. Treatment with 317.4µM Fumonisin B2 for 24 hours significantly induced cell death in HEK293 cells, promoted production of reactive oxygen species (ROS), and caused mitochondrial membrane depolarization [6].
In vivo, Fumonisin B2 treatment via oral administration at a dose of 1mg/kg/day for 3 days significantly exacerbated the inflammatory response in the atopic dermatitis (AD) mouse model, reduced epidermal water loss, and increased production of pro-inflammatory cytokines[7]. Oral administration of a 0.1mg/kg/day dose of Fumonisin B2 for 10 consecutive days significantly exacerbated the pathological process of psoriasis induced by imiquimod in mice[8].
References:
[1] Frisvad J C, Smedsgaard J, Samson R A, et al. Fumonisin B2 production by Aspergillus niger[J]. Journal of agricultural and food chemistry, 2007, 55(23): 9727-9732.
[2] Bondy G S, Barker M G, Lombaert G A, et al. A comparison of clinical, histopathological and cell-cycle markers in rats receiving the fungal toxins fumonisin B1 or fumonisin B2 by intraperitoneal injection[J]. Food and chemical toxicology, 2000, 38(10): 873-886.
[3] Dombrink-Kurtzman M A. Fumonisin and beauvericin induce apoptosis in turkey peripheral blood lymphocytes[J]. Mycopathologia, 2003, 156(4): 357-364.
[4] Shier W T, Abbas H K, Mirocha C J. Toxicity of the mycotoxins fumonisins B1 and B2 and Alternaria alternata f. sp. lycopersici toxin (AAL) in cultured mammalian cells[J]. Mycopathologia, 1991, 116(2): 97-104.
[5] Yu S, Jia B, Liu N, et al. Evaluation of the individual and combined toxicity of fumonisin mycotoxins in human gastric epithelial cells[J]. International Journal of Molecular Sciences, 2020, 21(16): 5917.
[6] Mohan J, Sheik Abdul N, Nagiah S, et al. Fumonisin B2 induces mitochondrial stress and mitophagy in human embryonic kidney (Hek293) cells—a preliminary study[J]. Toxins, 2022, 14(3): 171.
[7] Ando M, Yamaguchi H, Morimoto A, et al. Chronic oral exposure to low-concentration fumonisin B2 significantly exacerbates the inflammatory responses of allergies in mice via inhibition of IL-10 release by regulatory T cells in gut-associated lymphoid tissue[J]. Archives of Toxicology, 2023, 97(10): 2707-2719.
[8] Ando M, Yamaguchi H, Iwashita N, et al. Oral Exposure to Low Concentration of Fumonisin B2, but Not Fumonisin B1, Significantly Exacerbates the Pathophysiology of Imiquimod-Induced Psoriasis in Mice[J]. International Journal of Molecular Sciences, 2024, 25(14): 7852.