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

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-beta 1/Smad2/3 signalling pathway, and also activated PPAR-gamma expression in rats and H9C2 cells. Further application of PPAR-gamma agonist (pioglitazone) and antagonist (GW9662) in H9C2 cells revealed that the up-regulation of PPAR-gamma expression induced by T-2 toxin is a self-preservation phenomenon, and increasing exogenous PPAR-gamma can alleviate the increase in TGF-beta 1 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-gamma and that PPAR-gamma has the potential to serve as an effective therapeutic target in T-2 toxin-induced cardiac fibrosis of rats.

Automated summary

T-2 toxin may induce cardiac fibrosis by activating the TGF-beta 1/Smad2/3 signaling pathway and increasing PPAR-gamma expression, and increasing exogenous PPAR-gamma can alleviate the cardiac fibrosis caused by T-2 toxin.