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Vascular apoptosis associated with meglumine antimoniate: In vivo investigation of a chick embryo model.
- Source :
-
Biochemical & Biophysical Research Communications . Nov2018, Vol. 505 Issue 3, p794-800. 7p. - Publication Year :
- 2018
-
Abstract
- Abstract 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. Highlights • Meglumine antimoniate possesses vascular apoptotic effect. • Meglumine antimoniate alters expression of apoptotic-regulating genes. • Induction of apoptotic signaling pathways lead to vascular defect during pregnancy. • Meglumine antimoniate induces embryo malformation. • Physicians should limit the use of meglumine antimoniate during embryo development. [ABSTRACT FROM AUTHOR]
- Subjects :
- *APOPTOSIS
*CHICKEN embryos
*BAX protein
*LEISHMANIASIS
*CASPASES
*P53 protein
Subjects
Details
- Language :
- English
- ISSN :
- 0006291X
- Volume :
- 505
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Biochemical & Biophysical Research Communications
- Publication Type :
- Academic Journal
- Accession number :
- 132576967
- Full Text :
- https://doi.org/10.1016/j.bbrc.2018.09.152