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小豆蔻水提物对阿霉素诱导大鼠心脏毒性的改善作用。

Ameliorative Effect of Cardamom Aqueous Extract on Doxorubicin-Induced Cardiotoxicity in Rats.

机构信息

Department of Histology, Faculty of Medicine, Kafrelsheikh University, Kafr El Sheikh, Egypt.

Department of Anatomy, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafr El Sheikh, Egypt,

出版信息

Cells Tissues Organs. 2018;206(1-2):62-72. doi: 10.1159/000496109. Epub 2019 Feb 4.

Abstract

This study was conducted to evaluate the potential cardioprotective effect of cardamom (CAR) against myocardial injuries induced by doxorubicin (DOX) in rats through investigation of histological alterations and the associated oxidative stress, apoptosis, inflammation, and angiogenesis. This study included 30 adult male albino rats that were randomized to 3 groups (n = 10/group): group I (control), group II (DOX) rats injected with DOX (2.5 mg/kg body weight [BW] i.p.) every other day for 2 weeks, and group III (CAR+DOX) received CAR extract (200 mg/kg BW) orally for 3 weeks, and 1 week later (starting from the 2nd week) they were injected with DOX (2.5 mg/kg BW i.p.) every other day for 2 weeks. Rats treated with DOX alone exhibited notable myocardial damage (discontinuity and disorganization of cardiac muscle fibers, mononuclear cell infiltration, and apparent increases in collagen fiber deposition) accompanied by loss of function (revealed by elevated serum levels of lactate dehydrogenase, creatine kinase, and cardiac troponin), induction of oxidative stress (indicated by higher levels of nitric oxide and malon-dialdehyde, and lower levels of superoxide dismutase, catalase, and glutathione peroxidase), apoptosis (evidenced by high caspase 3 activity and immunostaining), and inflammation (marked by high cardiac NFκB level). However, administration of CAR not only ameliorated all deleterious effects of DOX but also induced angiogenesis, as indicated by a significant increase in VEGF immunoreactivity. These data indicate that CAR could relieve DOX-induced cardiotoxicity, at least in part, via reductions in oxidative stress, apoptosis, and inflammation and increased tissue regeneration via induction of angiogenesis. Therefore, CAR could be a promising cytoprotective agent against DOX cardiotoxicity.

摘要

这项研究旨在评估小豆蔻(CAR)对大鼠多柔比星(DOX)诱导的心肌损伤的潜在心脏保护作用,通过研究组织学改变以及相关的氧化应激、细胞凋亡、炎症和血管生成。该研究包括 30 只成年雄性白化大鼠,随机分为 3 组(每组 10 只):第 I 组(对照组)、第 II 组(DOX)大鼠每隔一天腹腔注射 DOX(2.5mg/kg 体重),连续 2 周;第 III 组(CAR+DOX)大鼠连续 3 周口服 CAR 提取物(200mg/kg BW),1 周后(第 2 周开始)每隔一天腹腔注射 DOX(2.5mg/kg BW),连续 2 周。单独用 DOX 处理的大鼠表现出明显的心肌损伤(心肌纤维连续性和组织排列紊乱、单核细胞浸润以及胶原纤维沉积明显增加),同时伴有功能丧失(通过血清乳酸脱氢酶、肌酸激酶和心肌肌钙蛋白水平升高显示)、氧化应激诱导(通过一氧化氮和丙二醛水平升高以及超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶水平降低显示)、细胞凋亡(通过 caspase 3 活性和免疫染色升高显示)和炎症(通过心脏 NFκB 水平升高显示)。然而,CAR 的给药不仅改善了 DOX 的所有有害影响,还诱导了血管生成,这表现为 VEGF 免疫反应性显著增加。这些数据表明,CAR 可以通过减少氧化应激、细胞凋亡和炎症以及通过诱导血管生成增加组织再生,从而缓解 DOX 引起的心脏毒性。因此,CAR 可能是一种有前途的 DOX 心脏毒性的细胞保护剂。

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