National Reference Laboratory of Veterinary Drug Residues (HZAU) and Ministry of Agriculture Key Laboratory for the Detection of Veterinary Drug Residues in Foods, Huazhong Agricultural University, Wuhan, China; Ministry of Agriculture Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, China.
Ministry of Agriculture Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, China.
Food Chem Toxicol. 2021 Jun;152:112183. doi: 10.1016/j.fct.2021.112183. Epub 2021 Apr 6.
T-2 toxin, the most virulent toxin produced by the Fusarium genus, is thought to be the main cause of fatal cardiomyopathy known as Keshan disease. However, the mechanisms of T-2 toxin-induced cardiac toxicity and possible targets for its treatment remain unclear. In the present study, male Wistar rats were administered with 2 mg/kg b. w. T-2 toxin (i.g.) and sacrificed on day 7 after exposure. The hematological indices (CK, LDH) and electrocardiogram were significantly abnormal, the ultrastructure of mitochondria in the heart was changed, and the percentage of collagen area was significantly increased in the T-2 toxin-treated group. Meanwhile, T-2 toxin activated the TGF-β1/Smad2/3 signalling pathway, and also activated PPAR-γ expression in rats and H9C2 cells. Further application of PPAR-γ agonist (pioglitazone) and antagonist (GW9662) in H9C2 cells revealed that the up-regulation of PPAR-γ expression induced by T-2 toxin is a self-preservation phenomenon, and increasing exogenous PPAR-γ can alleviate the increase in TGF-β1 caused by T-2 toxin, thereby playing a role in relieving cardiac fibrosis. These findings for the first time demonstrate that T-2 toxin can regulate the expression of PPAR-γ and that PPAR-γ has the potential to serve as an effective therapeutic target in T-2 toxin-induced cardiac fibrosis of rats.
T-2 毒素是镰刀菌属产生的最具毒性的毒素，被认为是导致致命性心肌病（克山病）的主要原因。然而，T-2 毒素诱导心脏毒性的机制以及其治疗的可能靶点仍不清楚。在本研究中，雄性 Wistar 大鼠经口给予 2mg/kg b.w. T-2 毒素（ig），并在暴露后第 7 天处死。T-2 毒素处理组大鼠的血液学指标（CK、LDH）和心电图明显异常，心脏线粒体的超微结构发生改变，胶原面积百分比明显增加。同时，T-2 毒素激活了 TGF-β1/Smad2/3 信号通路，并在大鼠和 H9C2 细胞中激活了 PPAR-γ 的表达。进一步在 H9C2 细胞中应用 PPAR-γ 激动剂（吡格列酮）和拮抗剂（GW9662）表明，T-2 毒素诱导的 PPAR-γ 表达上调是一种自我保护现象，增加外源性 PPAR-γ 可以减轻 T-2 毒素引起的 TGF-β1 的增加，从而在缓解心脏纤维化方面发挥作用。这些发现首次表明 T-2 毒素可以调节 PPAR-γ 的表达，并且 PPAR-γ 有可能成为 T-2 毒素诱导大鼠心脏纤维化的有效治疗靶点。
