Protective effects of metallothionein induced by zinc against doxorubicin-caused cardiotoxicity and its potential mechanisms
- VernacularTitle:锌诱导金属硫蛋白表达对多柔比星心脏毒性的保护作用及其机制
- Author:
Jiabin GUO
;
Shuangqing PENG
;
Mifeng LIU
;
Changhui YAN
;
Haiying YANG
;
Guoqiang WANG
- Publication Type:Journal Article
- Keywords:
metallothionein;
doxorubicin;
oxidative stress;
zinc;
cardiotoxicity
- From:
Chinese Journal of New Drugs and Clinical Remedies
2007;26(2):81-86
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To investigate the effects of metallothionein (MT) induced by zinc on doxorubicin (DOX)-treated mice and to explore the potential mechanisms. METHODS: Male C57BL/6J mice were divided randomly into 4 groups (n = 6) following control, DOX, Zn and Zn plus DOX. Mice were pretreated with eikg-1, ip) or equal volume of saline, and were killed on d 4 after the last injection. Serum and hearts were collected for examination. RESULTS: Zinc pretreatment elevated cardiac MT levels significantly while other antioxidants in heart including glutathione (GSH), glutathione peroxidase (GSHpx) , superoxide dismutase (SOD), and catalase (CAT) were not altered. Severe oxidative injury occurred in the mice treated with DOX as myocardial lipid peroxidation and morphological changes manifested by myocardial fibers swelling and vacuolization and nuclear condensation or dissolution, with increased activities of serum creatine kinase and lactate dehydrogenase and depletion of GSH, GSHpx, and SOD while CAT activity was increased in compensation. However, pre-induction of MT with zinc attenuated all of these toxic changes significantly. Furthermore, DOX induced elevation of hydrogen peroxide in heart tissues was greatly inhibited by zinc pretreatment. CONCLUSION: Preinduction of MT by zinc protects the heart from DOX-induced cardiotoxicity, and this effect is possibly correlated with the property of MT on scavenging free radicals in vivo.
