Comparison of cytotoxicity of Miltefosine and its niosomal form on chick embryo model

Fatemeh Seyedi, Iraj Sharifi, Ahmad Khosravi, Elaheh Molaakbari, Hadi Tavakkoli, Ehsan Salarkia, Sina Bahraminejad, Mehdi Bamorovat, Shahriar Dabiri, Zohreh Salari, Ali Kamali, Guogang Ren

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Abstract

Various drugs have been used for the treatment of leishmaniasis, but they often have adverse effects on the body's organs. In this study, we aimed to explore the effects of one type of drug, Miltefosine (MIL), and its analogue or modifier, liposomal Miltefosine (NMIL), on several fetal organs using both in silico analysis and practical tests on chicken embryos. Our in silico approach involved predicting the affinities of MIL and NMIL to critical proteins involved in leishmaniasis, including Vascular Endothelial Growth Factor A (VEGF-A), the Kinase insert domain receptor (KDR1), and apoptotic-regulator proteins (Bcl-2-associate). We then validated and supported these predictions through in vivo investigations, analyzing gene expression and pathological changes in angiogenesis and apoptotic mediators in MIL- and NMIL-treated chicken embryos. The results showed that NMIL had a more effective action towards VEGF-A and KDR1 in leishmaniasis, making it a better candidate for potential operative treatment during pregnancy than MIL alone. In vivo, studies also showed that chicken embryos under MIL treatment displayed less vascular mass and more degenerative and apoptotic changes than those treated with NMIL. These results suggest that NMIL could be a better treatment option for leishmaniasis during pregnancy.
Original languageEnglish
Article number2482
Pages (from-to)1-16
Number of pages16
JournalScientific Reports
Volume14
Issue number1
Early online date30 Jan 2024
DOIs
Publication statusPublished - 30 Jan 2024

Keywords

  • Animals
  • Antiprotozoal Agents/pharmacology
  • Chick Embryo
  • Leishmaniasis, Visceral/drug therapy
  • Phosphorylcholine
  • Vascular Endothelial Growth Factor A/genetics

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