花萼和柑橘提取物对阿霉素诱导的小鼠心脏毒性的心脏保护作用。
The cardioprotective properties of Persicaria maculosa and Citrus sinensis extracts against doxorubicin-induced cardiotoxicity in mice.
发表日期:2024
作者:
Mohammad Mohammad Zaki, Ibrahim Helmi El-Sayed, Mamdouh Abdel-Mogib, Ashraf Abdel-Hameed El-Shehawy, Omali Youssef El-Khawaga
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
本研究评估了花萼 (PME) 和柑橘 (CME) 氢甲醇提取物以及柑橘水提取物 (CWE) 对阿霉素 (DOX) 诱导的心脏毒性的心脏保护特性。对提取物进行了表征。将小鼠分为八组:对照组(盐水)、DOX、保护组(注射 200 mg/kg 的 PME、CWE 或 CME,持续 21 天,口服和 DOX)和提取物(PME、CWE 或 CME 给药,口服、 21 天)。在实验第 8、13 和 18 天注射 DOX(5 mg/kg,腹膜内)。心脏肿瘤坏死因子-α (TNF-α)、核因子(红细胞衍生 2)样 2 (Nrf2) 和羰基还原酶 1 (CBR1) 表达水平,以及超氧化物歧化酶、过氧化氢酶、丙二醛、一氧化氮和总蛋白水平进行了评估。检测血清乳酸脱氢酶、肌酸磷酸激酶心脏同工酶、天冬氨酸转氨酶、胆固醇、甘油三酯和肌酐水平以及心脏组织。与对照相比,DOX显着上调(p<0.01)TNF-α表达,丙二醛,一氧化氮、心肌酶、脂质和肌酐水平,同时显着(p<0.01)下调 Nrf2 和 CBR1。此外,DOX 还会干扰抗氧化酶的活性(p<0.01)。相反,受保护的组显示出 DOX 引起的心脏毒性作用显着改善(p<0.01)。当前的研究为 P. maculosa 和 C. sinensis 的心脏保护机制提供了新的认识。这些提取物的心脏保护作用可能是由于它们的抗氧化活性、通过调节重要的抗氧化基因和主要抗氧化酶维持氧化还原稳态的能力,以及恢复炎症细胞因子和脂质水平的能力。值得注意的是,测试的提取物对正常小鼠没有显示出毒性变化。
This study assessed the cardioprotective properties of Persicaria maculosa (PME) and Citrus sinensis (CME) hydro-methanolic extracts, besides Citrus sinensis aqueous extract (CWE) against doxorubicin (DOX)-induced cardiotoxicity.The extracts were characterized. Mice were divided into eight groups: control (saline), DOX, protected (injected with 200 mg/kg of PME, CWE or CME for 21 days, orally, and DOX), and extracts (PME, CWE or CME administration, orally, for 21 days). DOX was injected (5 mg/kg, ip) on days 8, 13 and 18 of the experiment. Cardiac tumor necrosis factor-alpha (TNF-α), nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and carbonyl reductase 1 (CBR1) expression levels, besides superoxide dismutase, catalase, malondialdehyde, nitric oxide and total protein levels were evaluated. Serum lactate dehydrogenase, creatine phosphokinase cardiac isoenzyme, aspartate transaminase, cholesterol, triglycerides and creatinine levels, as well as the cardiac tissues were examined.Comparing with the control, DOX considerably (p<0.01) up-regulated TNF-α expression, malondialdehyde, nitric oxide, cardiac enzymes, lipids and creatinine levels, while it significantly (p<0.01) down-regulated Nrf2 and CBR1. Additionally, DOX interfered with antioxidant enzymes' activities (p<0.01). Conversely, protected groups showed a significant (p<0.01) amelioration of DOX-induced cardiotoxic effects.The current study provides a new understanding of P. maculosa and C. sinensis cardioprotective mechanisms. The extracts' cardioprotective effects may be due to their antioxidant activities, ability to maintain the redox homeostasis through regulation of important antioxidant genes and primary antioxidant enzymes, and capability to recover inflammatory cytokines and lipids levels. Noteworthy, the tested extracts showed no toxic changes on the normal mice.