姜黄素通过抑制氧化应激和调节 iNOS、NF-κB 和 TNF-α 减轻阿霉素诱导的大鼠心脏毒性和肝毒性。
Curcumin Ameliorates Doxorubicin-Induced Cardiotoxicity and Hepatotoxicity Via Suppressing Oxidative Stress and Modulating iNOS, NF-κB, and TNF-α in Rats.
机构信息
Department of Therapeutic Chemistry, National Research Centre, 33 El-Bohouth St., Dokki, Cairo, 12622, Egypt.
Pathology Department, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.
出版信息
Cardiovasc Toxicol. 2022 Feb;22(2):152-166. doi: 10.1007/s12012-021-09710-w. Epub 2021 Nov 27.
Doxorubicin (DOX) is one of the widely used anti-tumor drugs. However, DOX-induced cardiotoxicity (DIC) and hepatotoxicity (DIH) are among the side effects that limited its therapeutic efficiency and clinical applicability. This study aimed to investigate the cardioprotective and hepatoprotective potentials of curcumin (CMN)-a bioactive polyphenolic compound-in alleviating DOX-induced cardiotoxicity (DIC) and hepatotoxicity (DIH) in male rats. A single intraperitoneal (i.p.) dose of DOX (20 mg/kg) was used to induce DIC and DIH. DOX-intoxicated rats were co-treated with CMN (100 mg/kg, oral) for 10 days before and 5 days after a single dose of DOX. We studied the anti-inflammatory and anti-oxidative activities of CMN on biochemical and immunohistochemical aspects. DOX disrupted cardiac and hepatic functions and stimulated oxidative stress and inflammation in both tissues that was confirmed biochemically and immunohistochemically. DOX enhanced inflammatory interferon-gamma (IFN-γ) and upregulated immunoexpression of nuclear factor-κB (NF-κB), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-alpha (TNF-α). DOX induced structural alterations in both cardiac and hepatic tissues. CMN demonstrated cardioprotective potential through reducing cardiac troponin I (cTn1) and aspartate amino transaminase (AST). In addition, CMN significantly ameliorated liver function through decreasing alanine amino transaminase (ALT) and, gamma-glutamyl transferase (GGT), total cholesterol (TC), and triglycerides (TG). CMN demonstrated anti-inflammatory potential through decreasing IFN-γ levels and immunoexpression of iNOS, NF-κB, and TNF-α. Histopathologically, CMN restored DOX-associated cardiac and liver structural alterations. CMN showed anti-oxidative and anti-inflammatory potentials in both the cardiac and hepatic tissues. In addition, cTn1, IFN-γ, and AST could be used as blood-based biomarkers.
阿霉素（DOX）是一种广泛使用的抗肿瘤药物。然而，DOX 诱导的心脏毒性（DIC）和肝毒性（DIH）是限制其治疗效果和临床适用性的副作用之一。本研究旨在探讨姜黄素（CMN）-一种生物活性多酚化合物-在缓解雄性大鼠 DOX 诱导的心脏毒性（DIC）和肝毒性（DIH）中的心脏保护和肝脏保护潜力。单次腹腔（i.p.）给予 DOX（20mg/kg）诱导 DIC 和 DIH。在单次 DOX 剂量后 5 天，用 DOX （100mg/kg，口服）对 DOX 中毒大鼠进行 10 天的预处理和后处理。我们研究了 CMN 在生化和免疫组织化学方面的抗炎和抗氧化活性。DOX 破坏了心脏和肝脏功能，并在两种组织中刺激氧化应激和炎症，这在生化和免疫组织化学上得到了证实。DOX 增强了炎症性干扰素-γ（IFN-γ），并上调了核因子-κB（NF-κB）、诱导型一氧化氮合酶（iNOS）和肿瘤坏死因子-α（TNF-α）的免疫表达。DOX 引起了心脏和肝脏组织的结构改变。CMN 通过降低心肌肌钙蛋白 I（cTn1）和天冬氨酸氨基转移酶（AST）表现出心脏保护潜力。此外，CMN 通过降低丙氨酸氨基转移酶（ALT）、γ-谷氨酰转移酶（GGT）、总胆固醇（TC）和甘油三酯（TG），显著改善了肝功能。CMN 通过降低 IFN-γ水平和 iNOS、NF-κB 和 TNF-α的免疫表达表现出抗炎潜力。组织病理学上，CMN 恢复了 DOX 相关的心脏和肝脏结构改变。CMN 在心脏和肝脏组织中均表现出抗氧化和抗炎潜力。此外，cTn1、IFN-γ和 AST 可作为基于血液的生物标志物。
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