Grape Seed Proanthocyanidins Attenuates Doxorubicin-induced Cardiotoxicity by Regulating Nrf2/HO-1 Pathway
Objective:To observe grape seed proanthocyanidins could alleviate doxorubicin(DOX)-induced cardiotoxicity and the role of nuclear factor E2-related gene(Nrf2)/heme oxygenase-1(HO-1)pathway on it.Methods:The mice model with acute cardiotoxicity was established by DOX,and the experiment was divided into the control group(normal mice),grape seed proanthocyanidin group,DOX group,DOX+grape seed proanthocyanidin group,DOX+grape seed proanthocyanidin+ML385 group.Echocardiography was used to detect cardiac function in mice;hematoxylin-eosin(HE)staining was used to observe the pathological changes of myocardial cells in mice;the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)assay was used to detect the apoptosis of cardiomyocytes;enzyme-linked immunosorbent assay(ELISA)was used to measure serum creatine kinase isoenzyme(CK-MB),interleukin-6(IL-6),and interleukin-1β(IL-1β)levels;The kit was used to detect reactive oxygen species(ROS),malondialdehyde(MDA),and superoxide dismutase(SOD)levels in myocardial tissue;Western Blot was used to determine the expression levels of Nrf2/HO-1 pathway proteins.Results:Compared with the control group,the myocardial injury of the mice in the DOX group aggravated;the left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),serum CK-MB,IL-6,IL-1β levels,myocardial tissue ROS,MDA,myocardial cell apoptosis rate increased(P<0.05);ejection fraction(EF),fractional shortening(FS),myocardial tissue SOD,Nrf2,and HO-1 protein levels decreased(P<0.05).In the seed proanthocyanidin group,the difference in myocardial injury,LVESD,LVEDD,EF,FS,serum CK-MB,IL-6,IL-1βlevels,myocardial tissue ROS,MDA,SOD,Nrf2,HO-1 protein,and cardiomyocyte apoptosis rate was not statistically significant(P>0.05).Compared with the DOX group,the myocardial injury of the mice in the DOX+grape seed proanthocyanidin group alleviated;LVESD,LVEDD,serum CK-MB,IL-6,IL-1β levels,myocardial tissue ROS,MDA,and myocardial cell apoptosis rate reduced(P<0.05);EF,FS,protein levels of SOD,Nrf2,and HO-1 in myocardial tissue increased(P<0.05).Compared with the DOX+ grape seed proanthocyanidin group,myocardial injury in the DOX+ grape seed proanthocyanidin+ ML385 group aggravated;LVESD,LVEDD,Serum CK-MB,IL-6,IL-1βlevels,myocardial tissue ROS,MDA,and myocardial cell apoptosis rate increased(P<0.05);EF,FS,myocardial tissue SOD,Nrf2,and HO-1 protein levels decreased(P<0.05).Conclusion:Grape seed proanthocyanidins may protect against DOX-induced cardiotoxicity in mice by activating the Nrf2/HO-1 pathway.
grape seed proanthocyanidinsnuclear factor E2 related geneheme oxygenase 1doxorubicinexperimental study
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维普
