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

Abstract

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.

MgAl-LDH nanoflowers as a novel sensing material for high-performance humidity sensing

“…5,6 Owing to their unique composition and ion-exchange properties, LDHs are extensively utilized in various elds such as catalysis, drug delivery, wastewater treatment, and adsorption, demonstrating their versatility and applicability across diverse applications. [7][8][9][10] LDHs can be synthesized using diverse techniques such as co-precipitation, hydrothermal synthesis, and ion exchange. Their functionality can be tailored by adjusting the layered composition, interlayer anions, and conditions of synthesis, offering a high degree of versatility and customization.…”