Protective effects of agmatine on doxorubicin-induced chronic cardiotoxicity in rat

详细信息    查看全文

• 作者：Fatemeh Yarmohmmadi^a ; ^b ; Nastaran Rahimi^a ; ^b ; Hedyeh Faghir-Ghanesefat^a ; ^b ; Nina Javadian^a ; ^b ; Alireza Abdollahi^c ; Parvin Pasalar^d ; Farahnaz Jazayeri^a ; Shahram Ejtemaeemehr^a ; Ahmad Reza Dehpour^a ; ^b ; ^{dehpoura@sina.tums.ac.ir} ; ^{dehpour@yahoo.com}
• 关键词：Doxorubicin ; Agmatine ; Papillary muscle ; Cardiotoxicity ; ECG ; Rats
• 刊名：European Journal of Pharmacology
• 出版年：2017
• 出版时间：5 February 2017
• 年：2017
• 卷：796
• 期：Complete
• 页码：39-44
• 全文大小：930 K
• 卷排序：796

文摘

The detrimental cardio-toxic effect of doxorubicin, an effective chemotherapeutic agent, limited its clinical use. It has been claimed that doxorubicin cardio-toxicity occurs through calcium ions (Ca2+) overload and reactive oxygen species production. Agmatine, an endogenous imidazoline receptor agonist, induce uptake of cytosolic Ca2+ and cause an increase in activity of calcium pumps, including Ca2+-ATPase. Also it shows self-scavenging effect against reactive oxygen species production. Therefore, present study was designed to investigate the effects of agmatine against chronic cardio-toxicity of doxorubicin in rats.Male wistar rats were intraperitoneally injected with doxorubicin and agmatine four times a week for a month. Agmatine significantly alleviate the adverse effect of doxorubicin on left ventricular papillary muscle stimulation threshold and contractibility. Chronic co-administration of agmatine with doxorubicin blocked electrocardiographic changes induced by doxorubicin. In addition, agmatine improved body weight and decreased the mortality rate of animals by doxorubicin. Moreover, reversing the doxorubicin induced myocardial lesions was observed in animals treated by agmatine. A significant rise in the total antioxidant capacity of rat plasma was achieved in agmatine-treated animals in comparison to doxorubicin.To conclude, agmatine may improve therapeutic outcomes of doxorubicin since it exerts protective effects against doxorubicin-induced chronic cardiotoxicity in rats.