Sterigmatocystin

Sterigmatocystin is a mycotoxin produced by fungi of the genus Aspergillus^[1]. IC₅₀ of sterigmatocystin against P. falciparum transmission was about 16 μg/mL or 48 μM^[2]. Sterigmatocystin inhibited P. falciparum proliferation in the blood with an IC₅₀ of 34 µM and limited the sexual parasites to infect mosquitoes with an IC₅₀ of 48 µM^[2].

In vitro, treatment with 0.78, 1.56 and 3.12 μM sterigmatocystin in human neuroblastoma (SH-SY5Y) cells for 24h induced an increase in ROS (reactive oxygen species) generation and LPO (lipid peroxidation) as well as a depletion of GSH (antioxidant no-enzymatic) levels, an increase in GSSG (oxidized to glutathione disulphide) content and a decrease in GSH/GSSG ratio at the highest concentrations^[3]. In human gastric epithelial GES-1 cells, exposure to 3 µM of sterigmatocystin for 24 h induced DNA damage, which subsequently activated ATM-Chk2 and ATM-p53 signalling pathways resulting in G2 arrest^[4]. In vitro, treatment with 3 and 6 μM sterigmatocystin respectively for 1 h significantly increased more DNA strand breaks and the expression level of ROS (reactive oxygen species) and 8-OHdG (8-hydroxydeoxyguanosine) in HepG2 cells^[5].

In vivo, demonstrated that male Wistar rats were orally treated with a single sterigmatocystin dose (10, 20 and 40 mg/kg b.w.) increased the expression level of malondialdehyde (MDA; all sterigmatocystin doses) and catalase (CAT; 10 mg/kg b.w.) in plasma, decreased the expression level of glutathione peroxidase (GPx; 20 and 40 mg/kg b.w.) in the liver, and increased the expression level of MDA and superoxide dismutase (SOD) in kidneys (all sterigmatocystin doses)^[6].

 References:

[1] Zingales V, et al. Sterigmatocystin-induced cytotoxicity via oxidative stress induction in human neuroblastoma cells. Food Chem Toxicol. 2020 Feb;136:110956.

[2] Niu G, et al. Sterigmatocystin Limits Plasmodium falciparum Proliferation and Transmission. Pharmaceuticals (Basel). 2021 Nov 29;14(12):1238.

[3] Zingales V, et al. Sterigmatocystin-induced DNA damage triggers cell-cycle arrest via MAPK in human neuroblastoma cells. Toxicol Mech Methods. 2021 Sep;31(7):479-488.

[4] Dabelić S, et al. Sterigmatocystin, 5-Methoxysterigmatocistin, and Their Combinations Are Cytotoxic and Genotoxic to A549 and Hepg2 Cells and Provoke Phosphorylation of Chk2, but Not Fancd2 Checkpoint Proteins. Toxins (Basel). 2021 Jun 30;13(7):464.

[5] Gao W, et al. Sterigmatocystin-induced oxidative DNA damage in human liver-derived cell line through lysosomal damage. Toxicol In Vitro. 2015 Feb;29(1):1-7.

[6] Dubravka R, et al. Sterigmatocystin moderately induces oxidative stress in male Wistar rats after short-term oral treatment. Mycotoxin Res. 2020 May;36(2):181-191.