Tempol prevents isoprenaline-induced takotsubo syndrome via the reactive oxygen species/mitochondrial/anti-apoptosis /p38 MAPK pathway.

ABSTRACT

Takotsubo Syndrome (TS) is a kind of acute cardiac syndrome with a complex pathophysiological mechanism that remains to be elucidated. The relationship between TS and reactive oxygen species has received increasing attention over in recent years. Therefore, the relationship between TS and reactive oxygen species was investigated in vivo and in vitro. Isoprenaline (ISO) was used to induce TS and tempol (quercetin) was selected as a scavenger to eliminate reactive oxygen species in animal experiments, and echocardiography was used to determine the incidence of TS. The H9C2 cells were cultured with different reagents to investigate the detailed mechanism; Reactive oxygen species levels and mitochondrial function were evaluated. Cell apoptosis rate was analyzed by TUNEL staining and the proteins involved in the signaling pathways were examined by Western blotting. It was found that a high dose of tempol almost eliminated TS and protected the cardiac function. Moreover, tempol also decreased the reactive oxygen species levels and reduced lipid droplet deposition in myocardial tissue. In terms of the cultured cells, tempol preconditioning decreased reactive oxygen species production as well as lipid droplet deposition, and protected the mitochondrial function by reducing mitochondrial swelling, thereby maintaining the mitochondrial membrane potential (ΔΨm) at a level that was higher than that of controls. Furthermore, tempol could reduce cells apoptosis after ISO treatment and decrease the protein level of p38, which is a member of the MAPK family, which and thus plays an important role in regulating cells apoptosis. This antiapoptotic effect of tempol was similar to that of a control reagent, SB203580, which is a specific inhibitor of phospha-p38 (p-p38). This study demonstrated, for the first time, a sudden increase in reactive oxygen species and effects of the downstream cascades play core roles in the development of TS.