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黄芪多糖通过靶向氧化应激和细胞凋亡编码途径对替米考星诱导的大鼠心脏损伤的保护作用。

Protective potency of Astragalus polysaccharides against tilmicosin- induced cardiac injury via targeting oxidative stress and cell apoptosis-encoding pathways in rat.

机构信息

Animal Wealth Development Department, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.

Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44511, Egypt.

出版信息

Environ Sci Pollut Res Int. 2020 Jun;27(17):20861-20875. doi: 10.1007/s11356-020-08565-y. Epub 2020 Apr 4.

DOI:10.1007/s11356-020-08565-y
PMID:32246429
Abstract

Tilmicosin (Til) was purposed to be used in the treatment of a wide range of respiratory diseases in livestock. However, undesirable adverse effects, cardiac toxicity, in particular, may be associated with Til therapy. In the present study, the response of adult rats administered Til subcutaneously at different doses (10, 25, 50, 75, and 100 mg/kg b.w.; single injection) was evaluated. Astragalus polysaccharide (AP) at two doses (100 and 200 mg/kg b.w.; intraperitoneally) was investigated for its potential to counteract the cardiac influences, involving the oxidative stress-induced damage and apoptotic cell death, elicited by the Til treatment at a dose of 75 mg/kg b.w. in rats. Til induced mortalities and altered the levels of the biomarkers for the cardiac damage, particularly in the rats treated with the doses of 75 and 100 mg/kg b.w.; similarly, morphological alterations in cardiac tissue were seen at all studied doses. AP was found to cause a significant (P ˂ 0.05) decline in the levels of impaired cardiac injury markers (troponin, creatine phosphokinase, and creatine phosphokinase-MB), improvement in the antioxidant endpoints (total antioxidant capacity), and attenuation in the oxidative stress indices (total reactive oxygen species, 8-hydroxy-2-deoxyguanosine, lipid peroxides [malondialdehyde], and protein carbonyl), associated with a significant (P ˂ 0.05) modulation in the mRNA expression levels of the encoding genes (Bcl-2, Bax, caspase-3, P53, Apaf-1, and AIF), related to the intrinsic pathway of apoptotic cell death in the cardiac tissue. AP administration partially restored the morphological changes in the rat's heart. The highest protective efficacy of AP was recorded at a dose level of 200 mg/kg b.w. Taken together, these results indicated that AP is a promising cardioprotective compound capable of attenuating Til-induced cardiac impact by protecting the rat cardiac tissue from Til-induced apoptosis when administered concurrently with and after the Til injection.

摘要

替米考星(Til)旨在用于治疗家畜的多种呼吸道疾病。然而,替米考星治疗可能与不良的副作用,特别是心脏毒性有关。在本研究中,评估了皮下给予不同剂量(10、25、50、75 和 100mg/kg b.w.;单次注射)替米考星的成年大鼠的反应。黄芪多糖(AP)以两种剂量(100 和 200mg/kg b.w.;腹腔内)研究了其潜在的对抗心脏影响的作用,涉及由 75mg/kg b.w.替米考星治疗在大鼠中引起的氧化应激诱导的损伤和凋亡细胞死亡。替米考星诱导了死亡率,并改变了心脏损伤生物标志物的水平,特别是在接受 75 和 100mg/kg b.w.剂量治疗的大鼠中;同样,在所有研究剂量下都观察到心脏组织的形态改变。AP 被发现可显著(P ˂ 0.05)降低受损的心脏损伤标志物(肌钙蛋白、肌酸磷酸激酶和肌酸磷酸激酶-MB)的水平,改善抗氧化终点(总抗氧化能力),并减弱氧化应激指数(总活性氧、8-羟基-2-脱氧鸟苷、脂质过氧化物[丙二醛]和蛋白质羰基),与编码基因(Bcl-2、Bax、caspase-3、P53、Apaf-1 和 AIF)的 mRNA 表达水平的显著(P ˂ 0.05)调节相关,与心脏组织中凋亡细胞死亡的内在途径有关。AP 给药部分恢复了大鼠心脏的形态变化。AP 的最高保护效力在 200mg/kg b.w.的剂量水平下记录。总之,这些结果表明,AP 是一种有前途的心脏保护化合物,当与替米考星注射同时或之后给予时,能够通过保护大鼠心脏组织免受替米考星诱导的凋亡,减轻替米考星引起的心脏影响。

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