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Toxico-pathological effects of meglumine antimoniate on human umbilical vein endothelial cells

A. Khosravi, I. Sharifi, H. Tavakkoli, AR. Keyhani, A. Afgar, Z. Salari, M. Bamorovat, F. Sharifi, T. Khaleghi, RS. Varma, S. Dabiri, SN. Nematollahi-Mahani, A. Babaee, M. Mostafavi, M. Hakimi Parizi, A. Derakhshanfar, E. Salarkia,

. 2019 ; 56 (-) : 10-18. [pub] 20181230

Language English Country England, Great Britain

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc19011996

Leishmaniasis is one of the most important parasitic diseases after malaria. The standard treatment of leishmaniasis includes pentavalent antimonials (SbV); however, these drugs are associated with serious adverse effects. There have been very few studies pertaining to their side effects and mechanism of action in the fetus. This investigation examines the effects of meglumine antimoniate (MA) on the survival rate, angiogenesis and cellular apoptosis in the human umbilical vein endothelial cells (HUVECs). HUVECs were treated with varying doses of MA (100-800 μg/ml) for 24, 48 and 72 h and the survival rate was studied by colorimetric assay, flow cytometry, immunocytochemistry, migration (scratch) assay and tube formation assay. The results of quantitative real-time PCR (qPCR) studies indicated that the most important genes involved in presenting angiogenesis included VEGF and its receptors (Kdr and Flt-1), NP1 and Hif-1α genes including the anti-apoptotic gene of Bcl2, were significantly reduced compared to the control group (p < 0.05). In contrast, the most leading genes involved in the phenomenon of apoptosis were P53, Bax, Bak, Apaf-1 and caspases 3, 8 and 9, which were significantly up regulated compared to the control group (p < 0.05).

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$a Leishmaniasis is one of the most important parasitic diseases after malaria. The standard treatment of leishmaniasis includes pentavalent antimonials (SbV); however, these drugs are associated with serious adverse effects. There have been very few studies pertaining to their side effects and mechanism of action in the fetus. This investigation examines the effects of meglumine antimoniate (MA) on the survival rate, angiogenesis and cellular apoptosis in the human umbilical vein endothelial cells (HUVECs). HUVECs were treated with varying doses of MA (100-800 μg/ml) for 24, 48 and 72 h and the survival rate was studied by colorimetric assay, flow cytometry, immunocytochemistry, migration (scratch) assay and tube formation assay. The results of quantitative real-time PCR (qPCR) studies indicated that the most important genes involved in presenting angiogenesis included VEGF and its receptors (Kdr and Flt-1), NP1 and Hif-1α genes including the anti-apoptotic gene of Bcl2, were significantly reduced compared to the control group (p < 0.05). In contrast, the most leading genes involved in the phenomenon of apoptosis were P53, Bax, Bak, Apaf-1 and caspases 3, 8 and 9, which were significantly up regulated compared to the control group (p < 0.05).
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$a Sharifi, Iraj $u Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran. Electronic address: iraj.sharifi@yahoo.com.
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$a Tavakkoli, Hadi $u Department of Clinical Science, School of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran. Electronic address: tavakkoli@uk.ac.ir.
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$a Keyhani, Ali Reza $u Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran.
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$a Afgar, Ali $u Research Center for Hydatid Disease in Iran, Kerman University of Medical Sciences٫ Kerman, Iran.
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$a Salari, Zohreh $u Obstetrics & Gynecology Center, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
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$a Bamorovat, Mehdi $u Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran.
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$a Sharifi, Fatemeh $u Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran.
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$a Khaleghi, Tabandeh $u Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran.
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$a Varma, Rajender S $u Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University in Olomouc, Šlechtitelů 27, Olomouc 783 71, Czech Republic.
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$a Dabiri, Shahriar $u Afzalipour School of Medicine & Pathology and Stem Cells Research Center, Kerman University of Medical Sciences, Kerman, Iran.
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$a Nematollahi-Mahani, Seyed Noureddin $u Physiology Research Center, Kerman University of Medical Sciences, Kerman, Iran.
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$a Babaee, Abdolreza $u Anatomical Sciences Department, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
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$a Mostafavi, Mahshid $u Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran.
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$a Hakimi Parizi, Maryam $u Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran.
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$a Derakhshanfar, Amin $u Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.
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$a Salarkia, Ehsan $u Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran.
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