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Cardiac inflammation, necrosis, and fibrosis were determined by histological and immunohistochemical analyses. Cytokines in rat sera and cardiac tissue were detected by enzyme\u2010linked immunosorbent assay (ELISA) and quantitative real\u2010time (qRT)\u2010PCR. Rat macrophages cultured in the presence of TNE for 48\u2009h were harvested for flow cytometry, while supernatants were collected for cytokine and reactive oxygen species (ROS) measurement.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    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\u2010\n                    <jats:italic>\u03b1<\/jats:italic>\n                    , IFN\u2010\n                    <jats:italic>\u03b3<\/jats:italic>\n                    , and IL\u20106) and prooxidative parameters (NO\n                    <jats:sub>2<\/jats:sub>\n                    , O\n                    <jats:sub>2<\/jats:sub>\n                    , and H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ), while increased level of immunosuppressive IL\u201010 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\u2010treated animals. In vitro lipopolysaccharide (LPS)\u2010stimulated macrophages cultured in the presence of TNE adopted immunosuppressive phenotype characterized by decreased production of proinflammatory cytokines and prooxidative mediators.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    Our study provides the evidence that TNE ameliorates cisplatin\u2010induced cardiotoxicity in rats by reducing inflammation and oxidative stress via promoting M2 macrophage polarization.\n                  <\/jats:p>","DOI":"10.1155\/mi\/6587305","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T07:35:46Z","timestamp":1737531346000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<i>Trapa natans L<\/i>\n                    . Extract Attenuates Inflammation and Oxidative Damage in Cisplatin\u2010Induced Cardiotoxicity in Rats by Promoting M2 Macrophage Polarization"],"prefix":"10.1155","volume":"2025","author":[{"given":"Vesna","family":"Matovic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6759-2720","authenticated-orcid":false,"given":"Biljana","family":"Ljujic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1166-6137","authenticated-orcid":false,"given":"Ivana","family":"Radojevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3713-710X","authenticated-orcid":false,"given":"Gorica","family":"\u0110elic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5177-1521","authenticated-orcid":false,"given":"Marina Miletic","family":"Kovacevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8930-7775","authenticated-orcid":false,"given":"Suzana","family":"Zivanovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7970-4892","authenticated-orcid":false,"given":"Milos","family":"Papic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4518-1066","authenticated-orcid":false,"given":"Nevena","family":"Milivojevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2056-1158","authenticated-orcid":false,"given":"Ivica","family":"Petrovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8151-9004","authenticated-orcid":false,"given":"Marina","family":"Gazdic Jankovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,22]]},"reference":[{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2014.07.025"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2022.154331"},{"key":"e_1_2_9_3_2","first-page":"8007","article-title":"Kaempferol Attenuated Cisplatin-Induced Cardiac Injury via Inhibiting STING\/NF-Kappa B-Mediated Inflammation","volume":"12","author":"Qi Y. 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