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Updated: Dec 9, 2025
Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis
Published on: February 10, 2015
Protective Effects of Spermidine Against Cirrhotic Cardiomyopathy in Bile Duct-Ligated Rats
Mohammad Sheibani1, Sadaf Nezamoleslami, Seyyedeh E Mousavi
1*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.
Insights
Spermidine, an antioxidant polyamine, significantly improved cirrhotic cardiomyopathy in bile duct ligation (BDL) rats. The 10 mg/kg dose reduced inflammation and oxidative stress, enhancing cardiac function.
Area of Science:
- Cardiology
- Hepatology
- Pharmacology
Background:
- Cirrhotic cardiomyopathy is a major complication impacting liver transplantation outcomes.
- Bile duct ligation (BDL) in animal models mimics cirrhotic cardiomyopathy's pathophysiology.
- Inflammatory and oxidant markers are key contributors to cirrhotic cardiomyopathy.
Purpose of the Study:
- To investigate the therapeutic effects of spermidine on cirrhotic cardiomyopathy in a BDL rat model.
- To evaluate spermidine's impact on cardiac function, inflammation, and oxidative stress markers.
- To determine the optimal dosage of spermidine for mitigating cirrhotic cardiomyopathy.
Main Methods:
- Rats underwent bile duct ligation (BDL) and were treated with varying doses of spermidine (5, 10, 50 mg/kg) or placebo.
- Cardiac function was assessed via electrocardiography (ECG) and papillary muscle isolation.
- Serum and cardiac tissue levels of inflammatory markers (TNF-α, IL-1β, IL-10), oxidative stress markers (SOD, GSH, MDA), and NF-κB were analyzed.
Main Results:
- BDL rats exhibited significant cirrhotic cardiomyopathy signs compared to controls.
- Spermidine administration, particularly at 10 mg/kg, markedly improved cardiac condition.
- The 10 mg/kg spermidine dose reduced inflammatory mediators and increased antioxidant enzyme activity, with supportive histopathological findings.
Conclusions:
- Spermidine demonstrates significant therapeutic potential in ameliorating cirrhotic cardiomyopathy.
- A 10 mg/kg dose of spermidine effectively combats inflammation and oxidative stress in the BDL rat model.
- Spermidine represents a promising therapeutic agent for managing cirrhotic cardiomyopathy.
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 (Mg) 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 Mg and K. This study demonstrates that spermidine at the dose of 10 mg/kg significantly improved the cirrhotic cardiomyopathy in BDL model in rats.
