P3812
AMPK/PGC1 activation by melatonin attenuates acute doxorubicin cardiotoxicity

Extract

Doxorubicin (DOX) is a highly effective antineoplastic anthracycline drug; however, the adverse effect of the cardiotoxicity has limited its widespread application. Melatonin, a highly conserved molecule that is mainly produced by the pineal gland, is well known for its free radical scavenging and anti-oxidative roles. The aim of this study was to investigate the possible protective effects of melatonin against DOX-induced cardiomyopathy. We preliminarily established DOX-induced cardiotoxicity models in H9c2 cells, and C57 mice, which clearly showed cardiac dysfunction and injury, oxidative stress, and apoptotic damage. Treatment with melatonin obviously attenuated the DOX-induced cardiac dysfunction and pathological changes. The anti-oxidative stress activity of melatonin was achieved via reduced generation of reactive oxygen species through regulation of AMPK and PGC1α signaling. Its anti-apoptotic activity was shown by reductions in the number of TUNEL-positive cells and DNA fragments along with a decreased ratio of Bax/Bcl-2 expression. In a further mechanistic study, melatonin exerted improvement on the cardiac function, oxidative stress, and apoptosis were inhibited by Compound C treatment or AMPK/PGC1α siRNA.