Matovic Vesna, Ljujic Biljana, Radojevic Ivana, Đelic Gorica, Kovacevic Marina Miletic, Zivanovic Suzana, Papic Milos, Milivojevic Nevena, Petrovic Ivica, Gazdic Jankovic Marina
Faculty of Medical Sciences, Department of Genetics, University of Kragujevac, Kragujevac, Serbia.
Faculty of Medical Sciences, Center for Harm Reduction of Biological and Chemical Hazards, University of Kragujevac, Kragujevac, Serbia.
Mediators Inflamm. 2025 Jan 22;2025:6587305. doi: 10.1155/mi/6587305. eCollection 2025.
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.
罗勒属植物的果实和叶提取物具有广泛的免疫调节、抗炎和抗氧化作用；然而，它们对心脏保护的作用尚未得到研究。本研究旨在测试罗勒属植物提取物（TNE）对顺铂（CDDP）诱导的心脏毒性的生物学活性。将Wistar白化大鼠腹腔注射单次剂量的CDDP，并每天口服TNE，持续2周。通过组织学和免疫组织化学分析确定心脏炎症、坏死和纤维化情况。通过酶联免疫吸附测定（ELISA）和定量实时（qRT）-PCR检测大鼠血清和心脏组织中的细胞因子。将在TNE存在下培养48小时的大鼠巨噬细胞收获用于流式细胞术分析，同时收集上清液用于细胞因子和活性氧（ROS）测量。生化和组织病理学分析表明，TNE的应用显著减轻了CDDP诱导的心脏毒性。连续14天每天给予TNE可降低全身循环中促炎（TNF-、IFN-和IL-6）和促氧化参数（NO、O和HO）的水平，同时提高免疫抑制性IL-10以及抗氧化性谷胱甘肽（GSH）、过氧化氢酶（CAT）和超氧化物歧化酶（SOD）的水平。TNE治疗导致心脏炎症和纤维化减轻，同时CDDP处理动物心脏组织中巨噬细胞浸润减少，促炎和促纤维化基因的表达降低。在体外，在TNE存在下培养的脂多糖（LPS）刺激的巨噬细胞呈现出免疫抑制表型，其特征是促炎细胞因子和促氧化介质的产生减少。我们的研究提供了证据，表明TNE通过促进M2巨噬细胞极化来减轻炎症和氧化应激，从而改善大鼠顺铂诱导的心脏毒性。
