title: Protective effects of agmatine on doxorubicin-induced chronic cardiotoxicity in rat.
abstract: 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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Yarmohmmadi
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Nastaran
authors.initials: N
authors.lastname: Rahimi
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Hedyeh
authors.initials: H
authors.lastname: Faghir-Ghanesefat
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Nina
authors.initials: N
authors.lastname: Javadian
authors.affiliation: Department of Pathology, Imam Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Abdollahi
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Medical Sciences/University of Tehran, Tehran, Iran.
authors.forename: Parvin
authors.initials: P
authors.lastname: Pasalar
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Farahnaz
authors.initials: F
authors.lastname: Jazayeri
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Shahram
authors.initials: S
authors.lastname: Ejtemaeemehr
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: dehpoura@sina.tums.ac.ir.
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D066126:Cardiotoxicity / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D019610:Cytoprotection / Q000187:drug effects*; D004317:Doxorubicin / Q000009:adverse effects*; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D007501:Iron / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D000376:Agmatine; D004317:Doxorubicin; D007501:Iron
keywords: Agmatine; Cardiotoxicity; Doxorubicin; ECG; Papillary muscle; Rats