Original ArticleProtective Effects of Spermidine Against Cirrhotic Cardiomyopathy in Bile Duct-Ligated RatsSheibani, Mohammad MD*,†; Nezamoleslami, Sadaf Pharm D*,†; Mousavi, Seyyedeh E. PhD*; Faghir-Ghanesefat, Hedyeh MS†; Yousefi-Manesh, Hasan MS*,†; Rezayat, Seyed M. Pharm D, PhD*; Dehpour, Ahmadreza Pharm D, PhD*,†Author Information *Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; and †Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. Ahmad Reza Dehpour, Pharm D, PhD, Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 13145–784(e-mail: email@example.com). The authors report no conflicts of interest. Journal of Cardiovascular Pharmacology: September 2020 - Volume 76 - Issue 3 - p 286-295 doi: 10.1097/FJC.0000000000000872 Buy Metrics Abstract Cirrhotic cardiomyopathy is a critical factor that causes morbidity and mortality in crucial conditions such as liver transplantation. In animal model, the common pathophysiologic mechanisms of cirrhotic cardiomyopathy are similar to those associated with bile duct ligation (BDL). Overproduction of inflammatory and oxidant markers plays a crucial role in cirrhotic cardiomyopathy. Spermidine, a multifunctional polyamine, is known for its antioxidant and anti-inflammatory effects. In this study, we investigated the effects of spermidine on development of cirrhotic cardiomyopathy in BDL rats. Rats were randomly housed in 6 groups. Except the normal and sham groups, BDL was performed for all the control and spermidine groups. Seven days after operation, 3 different doses of spermidine (5, 10 and 50 mg/kg) were administrated until day 28, in spermidine groups. At the end of the fourth week, the electrocardiography (ECG) and papillary muscle isolation were performed. The serum level of tumor necrosis factor-a (TNF-α), interleukin-1β (IL-1β), and IL-10 and cardiac level of superoxide dismutase, glutathione (GSH). and malondialdehyde (MDA) were assessed. Furthermore, the nuclear factor-κB (NF-κB) expression was assessed by western blot. Cardiac histopathological changes were monitored. The serum levels of magnesium (Mg2+) and potassium (K+) were investigated. Control group, exhibited exaggerated signs of cirrhotic cardiomyopathy in comparison with the sham group. Co-administration of spermidine at the dose of 10 mg/kg in BDL rats significantly improved the cardiac condition, reduced the inflammatory mediators, and increased antioxidant enzymes. In addition, the histopathologic findings were in accordance with the other results of the study. Besides, there was no significant alteration in serum levels of Mg2+ and K+. This study demonstrates that spermidine at the dose of 10 mg/kg significantly improved the cirrhotic cardiomyopathy in BDL model in rats. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.