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Vascular apoptosis associated with meglumine antimoniate: In vivo investigation of a chick embryo model.

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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Khosravi A,Sharifi I,Tavakkoli H,Keyhani AR,Afgar A,Salari Z,Mosallanejad SS,Bamorovat M,Sharifi F,Hassanzadeh S,Sadeghi B,Dabiri S,Mortazaeizdeh A,Sheikhshoaie Z,Salarkia E

doi

10.1016/j.bbrc.2018.09.152

subject

Has Abstract

pub_date

2018-11-02 00:00:00

pages

794-800

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(18)32085-0

journal_volume

505

pub_type

杂志文章

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