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Updated: Jul 4, 2025
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
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[Spermidine alleviates lipopolysaccharide-induced myocardial injury in mice by suppressing apoptosis, ROS production
Objective:
To investigate the protective effect of spermidine against lipopolysaccharide (LPS)-induced myocardial injury in mice and the underlying mechanism.
Methods:
C57BL/6 mice subjected to intraperitoneal LPS injection with or without pretreatment with daily gavage of spermidine for 2 weeks were examined for myocardial pathologies using HE staining and transmission electron microscopy. In the cell experiment, cultured rat cardiomyocytes (H9c2 cells) were pretreated with 10 or 20 μmol/L spermidine before LPS exposure for 2 h, and the changes in cell viability and levels of lactate dehydrogenase (LDH) and cardiac troponin Ⅰ (cTNI) were assessed using CCK-8 kit, LDH detection kit and ELISA, respectively. Western blotting was performed to detect the changes in the expressions of Bax, Bcl-2, cleaved caspase-3, SLC7A11 and GPX4; the changes in reactive oxygen species (ROS) and Fe2+ levels were detected using fluorescent probes, and mitochondrial membrane potential of the cells was measured using JC-1 staining.
Results:
Treatment of the mice with LPS induced obvious myocardial and mitochondrial damages, which were significantly alleviated by pretreatment with spermidine. In H9c2 cells, LPS exposure significantly lowered the cell viability, increased LDH and cTNI levels and expressions of Bax and cleaved caspase-3 levels, decreased expressions of Bcl-2, SLC7A11 and GPX4, increased ROS production and Fe2+ level (P < 0.05), and lowered mitochondrial membrane potential (all P < 0.05). These effects were significantly alleviated by SPD pretreatment of the cells prior to LPS exposure.
Conclusion:
Spermidine alleviates LPS-induced myocardial injury by suppressing cell apoptosis and inhibiting cellular ROS production and ferroptosis.
Insights
Spermidine protects against lipopolysaccharide-induced myocardial injury by reducing cell death, oxidative stress, and ferroptosis. This study demonstrates spermidine
Area of Science:
- Cardiovascular Biology
- Cellular Toxicology
- Pharmacology
Context:
- Lipopolysaccharide (LPS) triggers significant myocardial and mitochondrial damage.
- LPS exposure in cardiomyocytes reduces viability and increases damage markers.
- Cellular stress pathways including apoptosis, ROS production, and ferroptosis are implicated in LPS-induced injury.
Purpose:
- To investigate the cardioprotective effects of spermidine against LPS-induced myocardial injury.
- To elucidate the underlying mechanisms involving apoptosis, reactive oxygen species (ROS), and ferroptosis.
Summary:
- Spermidine pretreatment significantly alleviated LPS-induced myocardial and mitochondrial damage in mice.
- In vitro, spermidine protected cardiomyocytes from LPS by improving cell viability and reducing LDH and cTNI levels.
- Spermidine inhibited apoptosis (Bax, cleaved caspase-3), reduced ROS and Fe2+ levels, and normalized mitochondrial membrane potential, while upregulating Bcl-2, SLC7A11, and GPX4.
Impact:
- Spermidine demonstrates significant therapeutic potential for mitigating LPS-induced myocardial injury.
- The findings highlight spermidine's role in suppressing key cell death pathways, including apoptosis and ferroptosis.
- This research provides mechanistic insights into spermidine's protective actions against sepsis-related cardiac complications.
