Cytotoxicity of Amphotericin B and AmBisome: In Silico and In Vivo Evaluation Employing the Chick Embryo Model
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...
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.860598/full |
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| author | Ahmad Khosravi Iraj Sharifi Hadi Tavakkoli Elaheh Molaakbari Sina Bahraminegad Ehsan Salarkia Fatemeh Seyedi Alireza Keyhani Zohreh Salari Fatemeh Sharifi Mehdi Bamorovat Ali Afgar Shahriar Dabiri |
| author_facet | Ahmad Khosravi Iraj Sharifi Hadi Tavakkoli Elaheh Molaakbari Sina Bahraminegad Ehsan Salarkia Fatemeh Seyedi Alireza Keyhani Zohreh Salari Fatemeh Sharifi Mehdi Bamorovat Ali Afgar Shahriar Dabiri |
| author_sort | Ahmad Khosravi |
| collection | DOAJ |
| description | 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 in silico and in vivo assays (chicken embryos). In vivo analysis was done by checking pathological changes, angiogenesis, and apoptosis alterations on eggs treated by Amp B and AmBisome. In silico 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. In vivo 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. |
| first_indexed | 2024-12-11T16:13:47Z |
| format | Article |
| id | doaj.art-ba14d43ffb774b57acb06911aa761eb6 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-11T16:13:47Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-ba14d43ffb774b57acb06911aa761eb62022-12-22T00:59:00ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-06-011310.3389/fphar.2022.860598860598Cytotoxicity of Amphotericin B and AmBisome: In Silico and In Vivo Evaluation Employing the Chick Embryo ModelAhmad Khosravi0Iraj Sharifi1Hadi Tavakkoli2Elaheh Molaakbari3Sina Bahraminegad4Ehsan Salarkia5Fatemeh Seyedi6Alireza Keyhani7Zohreh Salari8Fatemeh Sharifi9Mehdi Bamorovat10Ali Afgar11Shahriar Dabiri12Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, IranLeishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, IranDepartment of Clinical Science, School of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, IranDepartment of Chemistry, Shahid Bahonar University of Kerman, Kerman, IranLeishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, IranLeishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, IranDepartment of Anatomy, School of Medicine, Jiroft University of Medical, Sciences, Jiroft, IranLeishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, IranObstetrics and Gynecology Center, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, IranResearch Center of Tropical and Infectious Diseases Kerman University of Medical Sciences, Kerman, IranLeishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, IranResearch Center for Hydatid Disease in Iran, Kerman University of Medical Sciences, Kerman, IranAfzalipour School of Medicine and Pathology and Stem Cells Research Center, Kerman University of Medical Sciences, Kerman, IranLeishmaniasis 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 in silico and in vivo assays (chicken embryos). In vivo analysis was done by checking pathological changes, angiogenesis, and apoptosis alterations on eggs treated by Amp B and AmBisome. In silico 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. In vivo 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.https://www.frontiersin.org/articles/10.3389/fphar.2022.860598/fullleishmaniasisamphotericin Btoxicityapoptosisangiogenesisin silico |
| spellingShingle | Ahmad Khosravi Iraj Sharifi Hadi Tavakkoli Elaheh Molaakbari Sina Bahraminegad Ehsan Salarkia Fatemeh Seyedi Alireza Keyhani Zohreh Salari Fatemeh Sharifi Mehdi Bamorovat Ali Afgar Shahriar Dabiri Cytotoxicity of Amphotericin B and AmBisome: In Silico and In Vivo Evaluation Employing the Chick Embryo Model Frontiers in Pharmacology leishmaniasis amphotericin B toxicity apoptosis angiogenesis in silico |
| title | Cytotoxicity of Amphotericin B and AmBisome: In Silico and In Vivo Evaluation Employing the Chick Embryo Model |
| title_full | Cytotoxicity of Amphotericin B and AmBisome: In Silico and In Vivo Evaluation Employing the Chick Embryo Model |
| title_fullStr | Cytotoxicity of Amphotericin B and AmBisome: In Silico and In Vivo Evaluation Employing the Chick Embryo Model |
| title_full_unstemmed | Cytotoxicity of Amphotericin B and AmBisome: In Silico and In Vivo Evaluation Employing the Chick Embryo Model |
| title_short | Cytotoxicity of Amphotericin B and AmBisome: In Silico and In Vivo Evaluation Employing the Chick Embryo Model |
| title_sort | cytotoxicity of amphotericin b and ambisome in silico and in vivo evaluation employing the chick embryo model |
| topic | leishmaniasis amphotericin B toxicity apoptosis angiogenesis in silico |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.860598/full |
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