Vascular apoptosis associated with meglumine antimoniate: In vivo investigation of a chick embryo model
| Autor: | Saeid Hassanzadeh, Mehdi Bamorovat, Iraj Sharifi, Balal Sadeghi, Hadi Tavakkoli, Ehsan Salarkia, Zahra Sheikhshoaie, Alireza Keyhani, Shahriar Dabiri, Seyedeh Saedeh Mosallanejad, Zohreh Salari, Ahmad Khosravi, Abbas Mortazaeizdeh, Ali Afgar, Fatemeh Sharifi |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Vascular Endothelial Growth Factor A Embryo Nonmammalian Meglumine antimoniate Biophysics Extraembryonic Membranes Embryonic Development Apoptosis Chick Embryo Biology Biochemistry Andrology 03 medical and health sciences 0302 clinical medicine In vivo medicine Animals APAF1 Molecular Biology Meglumine Antimoniate Embryogenesis Embryo Cell Biology 030104 developmental biology Receptors Vascular Endothelial Growth Factor 030220 oncology & carcinogenesis Toxicity Apoptotic signaling pathway medicine.drug |
| Zdroj: | Biochemical and biophysical research communications. 505(3) |
| ISSN: | 1090-2104 |
| Popis: | The vasculo-toxic effect of meglumine antimoniate (MA) was confirmed in our previous investigation. The current study investigates the association of this effect with altered VEGF-A and VEGF-R2 expression. Additional mechanisms by which MA causes vascular toxicity are not clearly understood. We hypothesized that MA may alter normal expression of apoptotic genes and cause vascular toxicity. The current investigation was designed to address this issue using a chick embryo model. Fertile chicken eggs were treated with MA and the extra-embryonic membrane (EEM) vasculature was evaluated by morphometric, molecular and immunohistochemistry assays. The results showed that MA not only altered apoptotic gene expression, but that this alteration may disturb the normal development of the vascular network and cause embryo malformation. The relative expression level of the CASP3, CASP7, CASP9, APAF1, AIF1 and TP53 genes increased in drug-exposed EEMs. In addition, IHC assay confirmed the low expression BCL2 and increased expression of Bax, which are associated with a high rate of apoptosis. We suggest that induction of an apoptotic signaling pathway can lead to vascular defects during embryo development and the consecutive cascade of events can lead to the embryo malformation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect