2. Academic Validation
  3. PPAR-γ with its anti-fibrotic action could serve as an effective therapeutic target in T-2 toxin-induced cardiac fibrosis of rats

PPAR-γ with its anti-fibrotic action could serve as an effective therapeutic target in T-2 toxin-induced cardiac fibrosis of rats

  • Food Chem Toxicol. 2021 Jun;152:112183. doi: 10.1016/j.fct.2021.112183.
Qirong Lu 1,  Siyi Hu 2,  Pu Guo 1,  Xiaohui Zhu 1,  Zhongchang Ren 1,  Qinghua Wu 3,  Xu Wang 4
Affiliations

Affiliations

  • 1 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.
  • 2 Ministry of Agriculture Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, China.
  • 3 College of Life Science, Yangtze University, Jingzhou, 434025, China; Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic; Jingchu Food Research and Development Center, Yangtze University, Jingzhou, 434025, China.
  • 4 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. Electronic address: wangxu@mail.hzau.edu.cn.
PMID: 33836209 DOI: 10.1016/j.fct.2021.112183
Abstract

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.

Keywords

Cardiac fibrosis; PPAR-γ; T-2 toxin; TGF-β1; Therapeutic target.

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