NHC Key Laboratory of Etiology and Epidemiology(Harbin Medical University): No. 157, Health Care Road, Nangang District, Harbin, 150081, China; Key Laboratory of Etiology and Epidemiology, Education Bureau of Heilongjiang Province: No. 157, Health Care Road, Nangang District, Harbin, China.
Toxicon. 2024 Oct;249:108060. doi: 10.1016/j.toxicon.2024.108060. Epub 2024 Aug 6.
T-2 toxin is recognized as the most potent and prevalent secondary metabolite among monotrichous mycotoxins produced by Fusarium species. Multiple studies have substantiated the hepatotoxic effects of T-2 toxin. This study aimed to investigate whether NF-κB and NLRP3-mediated pyroptosis is involved in the underlying mechanism of T-2 toxin hepatotoxicity. We designed three groups of rat models, blank control; solvent control and T-2 toxin (0.2 mg/kg body weight/day), which were euthanized at week 8 after gavage staining of the toxin. Through HE staining and biochemical indicators associated with liver injury, we observed that T-2 toxin induced liver damage in rats. By Western blot analysis and qRT-PCR, we found that the expression levels of pyroptosis-related genes and proteins were significantly higher in the T-2 toxin group. In addition, we also found a significant increase in the expression of p-NF-κB protein, an upstream regulator of NLRP3. In conclusion, NF-κB and NLRP3-mediated pyroptosis may be involved in the mechanism of hepatotoxic action of T-2 toxin, which provides a new perspective.
T-2 毒素被认为是镰刀菌属产生的单端孢霉烯族次生代谢物中最有效和最普遍的一种。多项研究证实了 T-2 毒素的肝毒性作用。本研究旨在探讨 NF-κB 和 NLRP3 介导的细胞焦亡是否参与 T-2 毒素肝毒性的潜在机制。我们设计了三组大鼠模型,空白对照组;溶剂对照组和 T-2 毒素(0.2mg/kg 体重/天)组,在灌胃染毒 8 周后处死。通过 HE 染色和与肝损伤相关的生化指标,我们观察到 T-2 毒素诱导大鼠肝脏损伤。通过 Western blot 分析和 qRT-PCR,我们发现 T-2 毒素组细胞焦亡相关基因和蛋白的表达水平显著升高。此外,我们还发现 NLRP3 的上游调节因子 p-NF-κB 蛋白的表达也显著增加。综上所述,NF-κB 和 NLRP3 介导的细胞焦亡可能参与了 T-2 毒素的肝毒性作用机制,为这一问题提供了新的视角。