Toxico-pathological effects of meglumine antimoniate on human umbilical vein endothelial cells

Khosravi, Ahmad; Sharifi, Iraj; Tavakkoli, Hadi; Keyhani, Ali Reza; Afgar, Ali; Shahshahan, Zahra; Bamorovat, Mehdi; Sharifi, Farshad; Khaleghi, Tabandeh; Varma, Rajender S.; Dabiri, Shahriar; Nematollahi-Mahani, Seyed Noureddin; Babaee, Abdolreza; Mostafavi, Mahshid; Parizi, Maryam Hakimi; Derakhshanfar, Amin; Salarkia, Ehsan

doi:10.1016/j.tiv.2018.12.018

Cited by 11 publications

(8 citation statements)

References 39 publications

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“…The YSM and chick’s extra-embryonic membranes models have been used in various researches, and there is a growing repository of data (e.g. anatomical, pharmaceutical, physiological and genetic) that continues to expand the model for toxicological studies ( Zhou et al, 2013 ; Deshpande et al, 2018 ; Khosravi et al, 2019 ; Fonseca et al, 2021 ; Zhang et al, 2022 ). The chick embryo has also proven to be a manageable and reliable model for evaluating antidiabetic agents ( Haselgrübler et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

“…A pinpoint widow of 1 mm was drilled in the eggs (outer shell and shell membrane) into the air cell of the egg and the embryos were treated with direct inoculation on the internal shell membrane via a 50 ml syringe, Hamilton tool. This procedure of inoculation has been applied before ( Oosterbaan et al, 2012 ; Khosravi et al, 2019 ). After injection, the widow was closed with melted paraffin (Merck CO., Germany) and the embryonated eggs were returned to the incubator for better development.…”

Section: Methodsmentioning

confidence: 99%

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Empagliflozin induces apoptotic-signaling pathway in embryonic vasculature: In vivo and in silico approaches via chick’s yolk sac membrane model

Mosallanejad

Mahmoodi²,

Tavakkoli³

et al. 2022

Front. Pharmacol.

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The present investigation was conducted to evaluate the vascular-toxicity of empagliflozin (EMP) in embryonic vasculature. Firstly, the vascular-toxicity of the drug as well as its interaction with apoptotic regulator proteins was predicted via in silico approach. In the next step, the apoptotic-signaling pathway in embryonic vasculature was evaluated using a chick’s YSM model. In silico simulation confirmed vascular-toxicity of EMP. There was also an accurate affinity between EMP, Bax and Bcl-2 (−7.9 kcal/mol). Molecular dynamics assay revealed complex stability in the human body conditions. Furthermore, EMP is suggested to alter Bcl-2 more than BAX. Morphometric quantification of the vessels showed that the apoptotic activity of EMP in embryonic vasculature was related to a marked reduction in vessel area, vessel diameter and mean capillary area. Based on the qPCR and immunohistochemistry assays, enhanced expression level of BAX and reduced expression level of Bcl-2 confirmed apoptotic responses in the vessels of the YSM. We observed that induction of an apoptotic signal can cause the embryonic defect of the vascular system following EMP treatment. The acquired data also raised suspicions that alteration in apoptotic genes and proteins in the vasculature are two critical pathways in vascular-toxicity of EMP.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Empagliflozin induces apoptotic-signaling pathway in embryonic vasculature: In vivo and in silico approaches via chick’s yolk sac membrane model

Mosallanejad

Mahmoodi²,

Tavakkoli³

et al. 2022

Front. Pharmacol.

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“…A tube formation assay was performed as previously described 25 . Matrigel (BD Biosciences) was solubilized overnight at 4°C.…”

Section: Methodsmentioning

confidence: 99%

“…A tube formation assay was performed as previously described. 25 Matrigel (BD Biosciences) was solubilized overnight at 4°C. Matrigel (50 μl) was added to each well of a 96-well plate and incubated at 37°C for 30 minutes.…”

Section: Tube Formation Assaymentioning

confidence: 99%

Antitumour metastasis and the antiangiogenic and antitumour effects of a Eimeria stiedae soluble protein

Huang

Yang

et al. 2021

Parasite Immunology

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Some protozoa (Plasmodium falciparum, Toxoplasma gondii, etc) are used to treat cancer because they can improve tumour‐induced immunosuppression. This study aims to evaluate the antitumour effect of Eimeria stiedae oocyst soluble protein (ESSP). ESSP was extracted, and mice were injected with 5 × 105 CT26 cells in the right axilla, and then, 50 μg of ESSP was intraperitoneally injected for 5 continuous days. The effect of ESSP on tumour immunity was detected by flow cytometry 25 days after the CT26 inoculation. The results showed that ESSP can inhibit the growth of CT26 subcutaneous tumours; significantly increase the expression of MHC I, MHC II, CD80 and CD86 on the surface of splenic dendritic cells; and enhance the level of IL‐12 secretion. ESSP induced an increase in the number of NK cells in the mouse spleen, and the levels of IFN‐γ and CD107 were upregulated in the NK cells and CD8+ T cells. The number of metastatic nodules in the lung tumours in the mice was significantly reduced, and the number of tubes, area of the loops and total length of the tubes were significantly reduced. ESSP enhances the antitumour immune response and inhibits tumour growth, metastasis and angiogenesis.

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“…Because of the importance of the angiogenesis process in many physiological and pathological processes, many researchers have studied angiogenesis in various laboratory models ( Eskander and Tewari, 2014 ; Maroof et al, 2014 ). The chorioallantoic membrane of chicken embryos is a suitable model for evaluating the process of angiogenesis and its factors on fetus growth and development ( Khosravi et al, 2019 ; Tavakkoli et al, 2019 ). The effects of medicine on the apoptotic process may also be used to evaluate the impact of a drug on embryonic health ( Khosravi et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity of Amphotericin B and AmBisome: In Silico and In Vivo Evaluation Employing the Chick Embryo Model

et al. 2022

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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.

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Toxico-pathological effects of meglumine antimoniate on human umbilical vein endothelial cells

Cited by 11 publications

References 39 publications

Empagliflozin induces apoptotic-signaling pathway in embryonic vasculature: In vivo and in silico approaches via chick’s yolk sac membrane model

Empagliflozin induces apoptotic-signaling pathway in embryonic vasculature: In vivo and in silico approaches via chick’s yolk sac membrane model

Antitumour metastasis and the antiangiogenic and antitumour effects of a Eimeria stiedae soluble protein

Cytotoxicity of Amphotericin B and AmBisome: In Silico and In Vivo Evaluation Employing the Chick Embryo Model

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