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两性霉素B和安必素的细胞毒性:以及采用鸡胚模型的评估

Cytotoxicity of Amphotericin B and AmBisome: and Evaluation Employing the Chick Embryo Model.

作者信息

Khosravi Ahmad, Sharifi Iraj, Tavakkoli Hadi, Molaakbari Elaheh, Bahraminegad Sina, Salarkia Ehsan, Seyedi Fatemeh, Keyhani Alireza, Salari Zohreh, Sharifi Fatemeh, Bamorovat Mehdi, Afgar Ali, Dabiri Shahriar

机构信息

Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran.

Department of Clinical Science, School of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran.

出版信息

Front Pharmacol. 2022 Jun 8;13:860598. doi: 10.3389/fphar.2022.860598. eCollection 2022.

DOI:10.3389/fphar.2022.860598
PMID:35754489
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9214246/
Abstract

Leishmaniasis has been identified as a significant disease in tropical and subtropical regions of the world, with Iran being one of the disease-endemic areas. Various treatments have been applied for this disease, and amphotericin B (Amp B) is the second line of treatment. Side effects of this drug have been reported in various organs. The present study investigated the effects of different types of Amp B on fetal organs using and assays (chicken embryos). analysis was done by checking pathological changes, angiogenesis, and apoptosis alterations on eggs treated by Amp B and AmBisome. approach was employed to predict the affinity of Amp B and AmBisome to the vascular endothelial growth factor A (VEGF-A), its receptor (KDR1), apoptotic-regulator proteins (Bcl-2-associated X protein (Bax), B-cell lymphoma (Bcl-2), and Caspase-8. The ADME-toxicity prediction reveals that AmBisome possesses a superior pharmacological effect to Amp B. The best result of all the dockings in the Molegro Virtual Docker (MVD) was obtained between Bax, Bcl-2, Caspase-8, KDR1, and VEGF-A targets. Due to the lower Egap (HOMO-LUMO) of AmBisome, the chemical reactivity of AmBisome was higher than that of Amp B. analysis showed that embryos that received Amp B exhibited less vascular density than AmBisome. Amp B alone significantly increased the expression of apoptosis and decreased angiogenesis genes compared to AmBisome. The histopathology analysis of the treated embryos showed a reduction in the blood vessel collapse and an increase in degenerative and apoptotic-necrotic changes in the embryonic tissues. Overall, the results suggest the potential benefits of AmBisome over Amp B, which might be a better treatment strategy to treat leishmaniasis during pregnancy.

摘要

利什曼病已被确认为世界热带和亚热带地区的一种重要疾病,伊朗是该疾病的流行地区之一。针对这种疾病已经应用了各种治疗方法,两性霉素B(Amp B)是二线治疗药物。该药物的副作用已在各个器官中被报道。本研究使用[具体实验方法1]和[具体实验方法2]检测(鸡胚),研究了不同类型的两性霉素B对胎儿器官的影响。通过检查经两性霉素B和两性霉素脂质体处理的鸡蛋的病理变化、血管生成和凋亡改变进行[具体分析方法]分析。采用[具体方法]预测两性霉素B和两性霉素脂质体对血管内皮生长因子A(VEGF-A)及其受体(KDR1)、凋亡调节蛋白(Bcl-2相关X蛋白(Bax)、B细胞淋巴瘤(Bcl-2)和半胱天冬酶-8)的亲和力。药物代谢动力学-毒性预测表明,两性霉素脂质体比两性霉素B具有更好的药理作用。在Molegro虚拟对接软件(MVD)中所有对接的最佳结果是在Bax、Bcl-2、半胱天冬酶-8、KDR1和VEGF-A靶点之间获得的。由于两性霉素脂质体的能隙(HOMO-LUMO)较低,其化学反应性高于两性霉素B。[具体分析方法]分析表明,接受两性霉素B处理的胚胎的血管密度低于两性霉素脂质体。与两性霉素脂质体相比,单独使用两性霉素B显著增加了凋亡表达并降低了血管生成基因。对处理后的胚胎进行组织病理学分析显示,血管塌陷减少,胚胎组织中的退行性和凋亡坏死变化增加。总体而言,结果表明两性霉素脂质体相对于两性霉素B具有潜在优势,这可能是孕期治疗利什曼病的更好治疗策略。

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