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

被引：42
作者：
Yarmohmmadi, Fatemeh [1 ,2 ]
Rahimi, Nastaran [1 ,2 ]
Faghir-Ghanesefat, Hedyeh [1 ,2 ]
Javadian, Nina [1 ,2 ]
Abdollahi, Alireza [3 ]
Pasalar, Parvin [4 ]
Jazayeri, Farahnaz [1 ]
Ejtemaeemehr, Shahram [1 ]
Dehpour, Ahmad Reza [1 ,2 ]
机构：
[1] Univ Tehran Med Sci, Fac Med, Dept Pharmacol, Tehran, Iran
[2] Univ Tehran Med Sci, Expt Med Res Ctr, Tehran, Iran
[3] Univ Tehran Med Sci, Imam Hosp, Dept Pathol, Tehran, Iran
[4] Med Sci Univ Tehran, Dept Biochem, Fac Med, Tehran, Iran
来源：
EUROPEAN JOURNAL OF PHARMACOLOGY | 2017年 / 796卷
关键词：
Doxorubicin; Agmatine; Papillary muscle; Cardiotoxicity; ECG; Rats; CONGESTIVE-HEART-FAILURE; IMIDAZOLINE RECEPTORS; MORPHINE; CELLS; CARDIOMYOPATHY; MECHANISMS; TOXICITY; CARDIOMYOCYTES; DYSFUNCTION; MODULATION;
D O I：
10.1016/j.ejphar.2016.12.022
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
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.
引用
收藏
页码：39 / 44
页数：6
相关论文
共 50 条
[21]   Clinical and preclinical modulation of chemotherapy-induced toxicity in patients with cancer [J].
Hoekman, K ;
van der Vijgh, WJF ;
Vermorken, JB .
DRUGS, 1999, 57 (02) :133-155
[22]  
Iqbal M, 2008, PHARMACOL REP, V60, P382
[23]  
JENSEN RA, 1984, J CARDIOVASC PHARM, V6, P186
[24]   DOXORUBICIN (ADRIAMYCIN) - A CRITICAL-REVIEW OF FREE RADICAL-DEPENDENT MECHANISMS OF CYTOTOXICITY [J].
KEIZER, HG ;
PINEDO, HM ;
SCHUURHUIS, GJ ;
JOENJE, H .
PHARMACOLOGY & THERAPEUTICS, 1990, 47 (02) :219-231
[25]   Morphine is protective against doxorubicin-induced cardiotoxicity in rat [J].
Kelishomi, Roohollah Babaei ;
Ejtemaeemehr, Shahram ;
Tavangar, Seyed Mohammad ;
Rahimian, Reza ;
Mobarakeh, Jalal Izadi ;
Dehpour, Ahmad Reza .
TOXICOLOGY, 2008, 243 (1-2) :96-104
[26]   Doxorubicin-induced apoptosis in endothelial cells and cardiomyocytes is ameliorated by nitrone spin traps and ebselen - Role of reactive oxygen and nitrogen species [J].
Kotamraju, S ;
Konorev, EA ;
Joseph, J ;
Kalyanaraman, B .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (43) :33585-33592
[27]  
Lee GT, 2003, J BIOCHEM MOL BIOL, V36, P251
[28]   Improving the therapeutic index of anthracycline chemotherapy: Focus on liposomal doxorubicin (Myocet™) [J].
Leonard, R. C. F. ;
Williams, S. ;
Tulpule, A. ;
Levine, A. M. ;
Oliveros, S. .
BREAST, 2009, 18 (04) :218-224
[29]  
Li Q, 2002, ACTA PHARMACOL SIN, V23, P219
[30]   AGMATINE ACTS AS AN ANTAGONIST OF NEURONAL NICOTINIC RECEPTORS [J].
LORING, RH .
BRITISH JOURNAL OF PHARMACOLOGY, 1990, 99 (01) :207-211
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