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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
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71b0/9214246/6864a43bcbb7/fphar-13-860598-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71b0/9214246/42e744974843/fphar-13-860598-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71b0/9214246/143abaa4b1a1/fphar-13-860598-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71b0/9214246/43a271a03e88/fphar-13-860598-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71b0/9214246/4239487fa00a/fphar-13-860598-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71b0/9214246/f39bcf526593/fphar-13-860598-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71b0/9214246/98269d0252fd/fphar-13-860598-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71b0/9214246/6fc43a13b73a/fphar-13-860598-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71b0/9214246/45be03dee830/fphar-13-860598-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71b0/9214246/b83dcfb9969e/fphar-13-860598-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71b0/9214246/6864a43bcbb7/fphar-13-860598-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71b0/9214246/42e744974843/fphar-13-860598-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71b0/9214246/143abaa4b1a1/fphar-13-860598-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71b0/9214246/43a271a03e88/fphar-13-860598-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71b0/9214246/4239487fa00a/fphar-13-860598-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71b0/9214246/f39bcf526593/fphar-13-860598-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71b0/9214246/98269d0252fd/fphar-13-860598-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71b0/9214246/6fc43a13b73a/fphar-13-860598-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71b0/9214246/45be03dee830/fphar-13-860598-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71b0/9214246/b83dcfb9969e/fphar-13-860598-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71b0/9214246/6864a43bcbb7/fphar-13-860598-g010.jpg

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本文引用的文献

[1]
Treatment of Complex Cutaneous Leishmaniasis with Liposomal Amphotericin B.

Pathogens. 2021-9-28

[2]
Visceral Leishmaniasis in pregnancy and vertical transmission: A systematic literature review on the therapeutic orphans.

PLoS Negl Trop Dis. 2021-8

[3]
Nanotechnology approaches for delivery and targeting of Amphotericin B in fungal and parasitic diseases.

Nanomedicine (Lond). 2021-4

[4]
Sixty years of Amphotericin B: An Overview of the Main Antifungal Agent Used to Treat Invasive Fungal Infections.

Infect Dis Ther. 2021-3

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The Problem with Amphotericin.

Clin Drug Investig. 2020-8

[6]
Old world cutaneous leishmaniasis in Iran: clinical variants and treatments.

J Dermatolog Treat. 2021-11

[7]
Vascular alteration in relation to fosfomycine: In silico and in vivo investigations using a chick embryo model.

Biomed Pharmacother. 2019-8-8

[8]
Host's immune response in unresponsive and responsive patients with anthroponotic cutaneous leishmaniasis treated by meglumine antimoniate: A case-control study of Th1 and Th2 pathways.

Int Immunopharmacol. 2019-2-14

[9]
Toxico-pathological effects of meglumine antimoniate on human umbilical vein endothelial cells.

Toxicol In Vitro. 2018-12-30

[10]
A single-group trial of end-stage patients with anthroponotic cutaneous leishmaniasis: Levamisole in combination with Glucantime in field and laboratory models.

Microb Pathog. 2018-12-21

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