Trapa natans L. Extract Attenuates Inflammation and Oxidative Damage in Cisplatin-Induced Cardiotoxicity in Rats by Promoting M2 Macrophage Polarization

菱角提取物通过促进 M2 巨噬细胞极化减轻大鼠顺铂诱发的心脏毒性引起的炎症和氧化损伤

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作者:Vesna Matovic, Biljana Ljujic, Ivana Radojevic, Gorica Đelic, Marina Miletic Kovacevic, Suzana Zivanovic, Milos Papic, Nevena Milivojevic, Ivica Petrovic, Marina Gazdic Jankovic

Background

Trapa natans L. fruits and leaf extracts have a broad range of immunomodulatory, anti-inflammatory, and antioxidant effects; however, their effects on cardiac protection have not been investigated.

Conclusion

Our study provides the evidence that TNE ameliorates cisplatin-induced cardiotoxicity in rats by reducing inflammation and oxidative stress via promoting M2 macrophage polarization.

Methods

Wistar albino rats received a single dose of CDDP intraperitoneally and TNE ones per day for 2 weeks orally. Cardiac inflammation, necrosis, and fibrosis were determined by histological and immunohistochemical analyses. Cytokines in rat sera and cardiac tissue were detected by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time (qRT)-PCR. Rat macrophages cultured in the presence of TNE for 48 h were harvested for flow cytometry, while supernatants were collected for cytokine and reactive oxygen species (ROS) measurement.

Objective

The study aims to test the biological activity of Trapa natans L. extract (TNE) in cisplatin (CDDP)-induced cardiotoxicity.

Results

Application of TNE significantly attenuated CDDP induced cardiotoxicity as demonstrated by biochemical and histopathological analysis. Administration of TNE once daily for 14 days decreased level of proinflammatory (TNF-α, IFN-γ, and IL-6) and prooxidative parameters (NO2, O2, and H2O2), while increased level of immunosuppressive IL-10 and antioxidative glutathione (GSH), catalase (CAT) and uperoxide dismutase (SOD) in the systemic circulation. TNE treatment resulted in attenuated heart inflammation and fibrosis accompanied with the reduced infiltration of macrophages and reduced expression of proinflammatory and profibrotic genes in heart tissue of CDDP-treated animals. In vitro lipopolysaccharide (LPS)-stimulated macrophages cultured in the presence of TNE adopted immunosuppressive phenotype characterized by decreased production of proinflammatory cytokines and prooxidative mediators.

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