[Protective effect of quercetin against adriamycin-induced cardiotoxicity and its mechanism in mice].
This study is to investigate the protective effect of quercetin against adriamycin-induced cardiotoxicity and its mechanism. The cardiotoxicity was induced by intraperitoneal injection of adriamycin (ADR) at a single dose of 20 mg x kg(-1). Mice were randomly divided into 5 groups (n=20): normal control group, ADR 20 mg x kg(-1) group, quercetin (50, 100, and 200 mg x kg(-1) groups, intragastric administration, once a day, for 7 days before ADR administration). The health conditions, electrocardiogram, activity of iNOS, SOD and LDH, levels of NO and MDA in serum or tissue homogenate, the ultrastructure and the expression of p53 protein in cardiac tissue of mice were observed. Compared with the normal control group, ADR decreased the amplitude of ECG's R wave (P < 0.001), increased the incidence of arrhythmia (to 60%), injured myocardial ultrastructure, increased the activity of LDH and iNOS, and levels of NO and MDA, decreased the activity of SOD, and increased the expression of p53 (P < 0.001). Compared with ADR 20 mg x kg(-1) group, the quercetin decreased the levels of LDH, iNOS, NO and MDA, increased the activity of SOD, restored the amplitude of R wave, decreased the incidence of arrhythmia and p53 expression (P < 0.001 , P < 0.01 or P < 0.05), and markedly reduced the myocardial ultrastructure injury. Quercetin had protective effect against adriamycin-induced cardiotoxicity. The mechanism may be related to its enhancing myocardial SOD activity, decreasing iNOS activity and inhibiting myocardial apoptosis.
Pei
Tian-xian
TX
Department of Pathophysiology, Harbin Medical University, Harbin 150086, China.
Xu
Chang-qing
CQ
Li
Bin
B
Zhang
Zhuo-ran
ZR
Gao
Xiu-xiang
XX
Yu
Jing
J
Li
Hong-zhu
HZ
Yang
Bao-feng
BF
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001145:Arrhythmias, Cardiac / Q000097:blood / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D004317:Doxorubicin; D005260:Female; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism*; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000648:ultrastructure; D009569:Nitric Oxide / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000097:blood; D020011:Protective Agents / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology*; D011897:Random Allocation; D013482:Superoxide Dismutase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D020011:Protective Agents; D016159:Tumor Suppressor Protein p53; D009569:Nitric Oxide; D008315:Malondialdehyde; D004317:Doxorubicin; D011794:Quercetin; D007770:L-Lactate Dehydrogenase; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase