Protective role of irisin against doxorubicin cardiotoxicity injury via PI3K/Akt signaling pathway

  AIM  To investigate whether irisin could regulate the PI3K/Akt signaling pathway to attenuate doxorubicin (Dox)-induced cardiotoxicity and its molecular mechanism.

  METHODS  H₉C₂ cells were cultured and randomly divided into the following groups: control (Con) group, irisin treatment (Irisin) group, Dox injury (Dox) group, Dox+Akt inhibitor (Dox+LY294002) group, irisin protection (Dox+Irisin) group, and Dox+Irisin+Akt inhibitor (Dox+Irisin+LY294002) group. TUNEL (TdT-mediated dUTP Nick-End Labeling), Western Blot and CCK-8 reagent were used to detect the apoptosis ratio, the expression of apoptotic related proteins and the cell viability respectively, which will further clarify the functions of irisin treatment against Dox-induced cardiotoxicity.

  RESULTS  The apoptosis rate of H₉C₂ cardiomyocytes was significantly increased after Dox treatment compared with the Con group. The expressions of Bax and Cleaved-caspase3 were significantly increased while the expression of Bcl-2 was significantly decreased (P<0.05), which were reversed by irisin treatment. In vitro experiments further demonstrated that irisin had a protective role against doxorubicin cardiotoxicity injury by increasing the phosphorylation of Akt, which was impaired by the PI3K inhibitor, LY294002.

  CONCLUSION  Irisin attenuates Dox-induced cardiotoxicity by the activation of PI3K/Akt signaling pathway, which may clinically provide new therapeutic targets and strategies against Dox-induced cardiotoxicity.