Protective role of Adiponectin on FoxO1-dependent autophagy against doxorubicin-induced cardiotoxicity

  AIM  To elucidate the mechanism of foxO1 signaling pathway in the protective role of adiponectin (APN) against doxorubicin-induced cardiotoxicity.

  METHODS  Neonatal rat cardiomyocytes (nrCMs) were randomly divided into the following groups: CON, APN, APN-DOX, DOX-Scramble siRNA, DOX-FoxO1 siRNA, APN-DOX-Scramble siRNA, and APN-DOX-FoxO1 siRNA. Cell viability was detected by CCK-8 kit, mitochondrial ATP production was detected by ATP detection kit, ROS production was detected by ROS detection kit, and autophagy marker protein expression was detected by Western blot.

  RESULTS  Compared with CON group, DOX treatment significantly decreased cell viability and mitochondrial ATP production but increased ROS production and activated autophagy (P<0.05). APN pretreatment significantly reduced DOX induced cardiotoxicity by inhibiting autophagy. In terms of the mechanism of the protective role of APN against Dox-induced cardiotoxicity, we found that APN inhibited the activation of autophagy by up-regulating the expression of phospho FoxO1, thus protecting nrCMs cells from DOX-induced cardiotoxicity. However, the myocardial protective effect of APN was abolished by FoxO1 siRNA treatment, such as the inhibition of autophagy and ATP production, and the increase of ROS production.

  CONCLUSION  APN attenuates DOX induced cardiotoxicity by up-regulating foxO1 phosphorylation and inhibiting autophagy activation.