T-2 Toxin is one of the most common and potent trichothecene mycotoxins, primarily produced by Fusarium species in grains and animal feed[1]. T-2 Toxin is a type A non-macrocyclic trichothecene toxin, and its toxic mechanism involves inhibiting protein synthesis by binding to peptidyl transferase[2]. T-2 Toxin can be metabolized in animals into hydrolysis products such as HT-2 Toxin and T-2 triol[3]. T-2 Toxin can cross the blood-brain barrier and accumulate in the central nervous system, thus producing significant neurotoxicity[4].
In vitro, treatment of neonatal rat primary cardiomyocytes with T-2 Toxin (0.25-1µM) for 24h induced cardiomyocyte damage and inhibited cell viability in a dose-dependent manner[5]. Treatment of rat ovarian granulosa cells with T-2 Toxin (1-100nM) for 24h inhibited cell growth, induced apoptosis, led to ROS accumulation, and decreased mitochondrial membrane potential in a dose-dependent manner[6].
In vivo, treatment of mice with T-2 Toxin (5.94mg/kg) via transdermal administration or T-2 Toxin (1.57mg/kg) via subcutaneous injection for 0-7 days both increased reactive oxygen species production, glutathione depletion, lipid peroxidation, and protein carbonyl content in mouse brain tissue in a time-dependent manner. Transdermal administration significantly increased the expression of superoxide dismutase and catalase, while subcutaneous administration significantly increased the expression of glutathione reductase and glutathione peroxidase[7].
References:
[1] Janik E, Niemcewicz M, Podogrocki M, et al. T-2 Toxin—The most toxic trichothecene mycotoxin: Metabolism, toxicity, and decontamination strategies[J]. Molecules, 2021, 26(22): 6868.
[2] Meneely J, Greer B, Kolawole O, et al. T-2 and HT-2 Toxins: toxicity, occurrence and analysis: a review[J]. Toxins, 2023, 15(8): 481.
[3] Li Y, Wang Z, Beier R C, et al. T-2 Toxin, a trichothecene mycotoxin: review of toxicity, metabolism, and analytical methods[J]. Journal of agricultural and food chemistry, 2011, 59(8): 3441-3453.
[4] Wang Y, Wang B, Wang P, et al. Review of neurotoxicity of T-2 Toxin[J]. Mycotoxin research, 2024, 40(1): 85-95.
[5] Xu J, Pan S, Gan F, et al. Selenium deficiency aggravates T-2 Toxin-induced injury of primary neonatal rat cardiomyocytes through ER stress[J]. Chemico-biological interactions, 2018, 285: 96-105.
[6] Wu J, Jing L, Yuan H, et al. T-2 Toxin induces apoptosis in ovarian granulosa cells of rats through reactive oxygen species-mediated mitochondrial pathway[J]. Toxicology letters, 2011, 202(3): 168-177.
[7] Chaudhary M, Rao P V L. Brain oxidative stress after dermal and subcutaneous exposure of T-2 Toxin in mice[J]. Food and Chemical Toxicology, 2010, 48(12): 3436-3442.
T-2 Toxin是最常见且毒性最强的单端孢霉烯类霉菌毒素之一，主要由镰刀菌属在谷物和饲料中产生[1]。T-2 Toxin是一种A类非大环三萜毒素，其毒性机制是通过结合肽转移酶来抑制蛋白质合成[2]。T-2 Toxin可在动物体内代谢转化为HT-2毒素、T-2-三醇等水解产物[3]。T-2 Toxin能够穿过血脑屏障并在中枢神经系统蓄积，从而产生显著的神经毒性[4]。
在体外，T-2 Toxin（0.25-1µM）处理新生大鼠原代心肌细胞24h，以剂量依赖性方式诱导了心肌细胞损伤，抑制了细胞活力[5]。T-2 Toxin（1-100nM）处理大鼠卵巢颗粒细胞24h，以剂量依赖性方式抑制了细胞的生长，诱导了细胞凋亡，导致细胞中ROS积累，降低了线粒体膜电位[6]。
在体内，T-2 Toxin（5.94mg/kg）通过经皮给药或者T-2 Toxin（1.57mg/kg）通过皮下注射给药处理小鼠0-7天，均以时间依赖性方式增加了小鼠脑组织中活性氧生成、谷胱甘肽消耗、脂质过氧化和蛋白质羰基含量，经皮给药途径中超氧化物歧化酶和过氧化氢酶的表达显著增加，而皮下给药途径中谷胱甘肽还原酶和谷胱甘肽过氧化物酶的表达显著增加[7]。