Inhibition of 12/15 lipoxygenase by baicalein reduces myocardial ischemia/reperfusion injury via modulation of multiple signaling pathways

• Published in: Apoptosis (London) 2014-04, Vol.19 (4), p.567-580
• Main Authors: Song, Lina, Yang, Hui, Wang, Hong-Xia, Tian, Cui, Liu, Yu, Zeng, Xiang-Jun, Gao, Erhe, Kang, Yu-Ming, Du, Jie, Li, Hui-Hua
• Format: Article
• Language: English
• Subjects: Acute Disease; Animals; Apoptosis - drug effects; Arachidonate 12-Lipoxygenase - metabolism; Arachidonate 15-Lipoxygenase - metabolism; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Biology; Cells, Cultured; Flavanones - pharmacology; Flavanones - therapeutic use; Hypertension; Inflammation - metabolism; Lipoxygenase Inhibitors - pharmacology; Lipoxygenase Inhibitors - therapeutic use; Mice; Mice, Inbred C57BL; Myocardial infarction; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Myocardial Infarction - prevention & control; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - prevention & control; Myocardium - metabolism; Myocardium - pathology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Oncology; Original Paper; Oxidative stress; Oxidative Stress - drug effects; Rats; Signal Transduction; Virology
• ISSN: 1360-8185; 1573-675X
• DOI: 10.1007/s10495-013-0946-z

12/15-Lipoxygenase (LOX) is a member of the LOX family that catalyzes the step from arachidonic acid to hydroxy-eicosatetraenoic acids (HETEs). Previous studies demonstrated that 12/15-LOX plays a critical role in the development of atherosclerosis, hypertension, heart failure, and other diseases; however, its role in myocardial ischemic injury was contraversal. Here, we investigated the inhibition of 12/15-LOX by baicalein on acute cardiac injury and dissected its molecular mechanism. In a mouse model of acute ischemia/reperfusion (I/R) injury, 12/15-LOX was significantly upregulated in the peri-infarct area surrounding the primary infarction. In cultured cardiac myocytes, baicalein suppressed apoptosis and caspase 3 activity in response to simulated ischemia/reperfusion (I/R). Moreover, administration of 12/15-LOX inhibitor, baicalein, significantly attenuated myocardial infarct size induced by I/R injury. Moreover, baicalein treatment significantly inhibited cardiomyocyte apoptosis, inflammatory responses and oxidative stress in the heart after I/R injury. The mechanisms underlying these effects were associated with the activation of ERK1/2 and AKT pathways and inhibition of activation of p38 MAPK, JNK1/2, and NF-kB/p65 pathways in the I/R-treated hearts and neonatal cardiomyoctes. Our data indicated that 12/15-LOX inhibitor baicalein can prevent myocardial I/R injury by modulation of multiple mechanisms, and suggest that baicalein could represent a novel therapeutic drug for acute myocardial infarction.