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.
甾体半胱氨酸是由曲霉属真菌产生的一种霉菌毒素[1]。甾体半胱氨酸对恶性疟原虫传播的IC50约为16 μg/mL或48 μM[2]。甾体半胱氨酸抑制恶性疟原虫在血液中的增殖,IC50为34 μM,限制有性寄生虫感染蚊子,IC50为48 μM[2]。
体外试验表明,用0.78、1.56和3.12 μM的甾体半胱氨酸在人类神经母细胞瘤（SH-SY5Y）中处理24小时,诱发ROS（活性氧）生成和LPO（脂质过氧化）增加,以及GSH（抗氧化剂无酶）水平耗尽,GSSG（氧化为谷胱甘肽二硫化物）含量增加,最高浓度时GSH/GSSG比例下降[3]。在人类胃上皮细胞GES-1中,暴露于3 µM的甾体半胱氨酸24小时诱发DNA损伤,随后激活ATM-Chk2和ATM-p53信号通路,导致G2停滞[4]。在体外,用3和6μM的甾体半胱氨酸处理1小时,可显著增加HepG2细胞中更多的DNA链断裂以及ROS（活性氧）和8-OHdG（8-羟基脱氧鸟苷）的表达水平[5]。
体内药效试验表明,雄性Wistar大鼠口服单一剂量的甾体半胱氨酸（10、20和40 mg/kg b.w.）后,血浆中丙二醛（MDA）和过氧化氢酶（CAT；10mg/kg b.w.）的表达水平增加,过氧化氢酶（CAT）；10 mg/kg b.w.）,肝脏中谷胱甘肽过氧化物酶（GPx；20和40 mg/kg b.w.）的表达水平下降,肾脏中MDA和超氧化物歧化酶（SOD）的表达水平上升[6]。