Protection against Doxorubicin-Induced Cytotoxicity by Geniposide Involves AMPKα Signaling Pathway.
Yan-Yan MengYu-Pei YuanXin ZhangChun-Yan KongPeng SongZhen-Guo MaQi-Zhu TangPublished in: Oxidative medicine and cellular longevity (2019)
Oxidative stress and cardiomyocyte apoptosis play critical roles in the development of doxorubicin- (DOX-) induced cardiotoxicity. Our previous study found that geniposide (GE) could inhibit cardiac oxidative stress and apoptosis of cardiomyocytes but its role in DOX-induced heart injury remains unknown. Our study is aimed at investigating whether GE could protect against DOX-induced heart injury. The mice were subjected to a single intraperitoneal injection of DOX (15 mg/kg) to induce cardiomyopathy model. To explore the protective effects, GE was orally given for 10 days. The morphological examination and biochemical analysis were used to evaluate the effects of GE. H9C2 cells were used to verify the protective role of GE in vitro. GE treatment alleviated heart dysfunction and attenuated cardiac oxidative stress and cell loss induced by DOX in vivo and in vitro. GE could activate AMP-activated protein kinase α (AMPKα) in vivo and in vitro. Moreover, inhibition of AMPKα could abolish the protective effects of GE against DOX-induced oxidative stress and apoptosis. GE could protect against DOX-induced heart injury via activation of AMPKα. GE has therapeutic potential for the treatment of DOX cardiotoxicity.
Keyphrases
- oxidative stress
- diabetic rats
- high glucose
- induced apoptosis
- protein kinase
- heart failure
- cell cycle arrest
- signaling pathway
- endoplasmic reticulum stress
- skeletal muscle
- dna damage
- cell death
- ischemia reperfusion injury
- endothelial cells
- drug induced
- type diabetes
- stem cells
- hydrogen peroxide
- metabolic syndrome
- insulin resistance
- stress induced
- heat shock protein