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

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. The study aims to test the biological activity of L. extract (TNE) in cisplatin (CDDP)-induced cardiotoxicity. 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. 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-, IFN-, and IL-6) and prooxidative parameters (NO, O, and HO), 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. Our study provides the evidence that TNE ameliorates cisplatin-induced cardiotoxicity in rats by reducing inflammation and oxidative stress via promoting M2 macrophage polarization.