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Current Molecular Pharmacology

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ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

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Research Article

Dapagliflozin Protects H9c2 Cells Against Injury Induced by Lipopolysaccharide via Suppression of CX3CL1/CX3CR1 Axis and NF-κB Activity

Author(s): Yousef Faridvand, Maryam Nemati, Elham Zamani-Gharehchamani, Hamid Reza Nejabati, Arezoo Rezaie Nezhad Zamani, Samira Nozari, Nasser Safaie, Mohammad Nouri and Ahmadreza Jodati*

Volume 15, Issue 6, 2022

Published on: 13 January, 2022

Article ID: e081021197099 Pages: 8

DOI: 10.2174/1874467214666211008142347

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Abstract

Background: Dapagliflozin, a selective Sodium-glucose cotransporter-2 (SGLT2) inhibitor, has been shown to play a key role in the control and management of metabolic and cardiac diseases.

Objective: The current study aims to address the effects of dapagliflozin on the expression of fractalkine (FKN), known as CX3CL1, and its receptors CX3CR1, Nuclear factor-kappa B(NF-κB) p65 activity, Reactive oxygen species (ROS), and inflammation in LPS-treated H9c2 cell line.

Methods: H9c2 cells were cultured with lipopolysaccharide (LPS) to establish a model of LPS-induced damage, and then, subsequently were treated with dapagliflozin for 72 h. Our work included measurement of cell viability (MTT), Malondialdehyde (MDA), intracellular ROS, tumor necrosis factor-α (TNF-α), NF-κB activity, and expression of CX3CL1/CX3CR1.

Results: The results showed that LPS-induced reduction of cell viability was successfully rescued by dapagliflozin treatment. The cellular levels of MDA, ROS, and TNF-α, as an indication of cellular oxidative stress and inflammation, were significantly elevated in H9c2 cells compared to the control group. Furthermore, dapagliflozin ameliorated inflammation and oxidative stress through the modulation of the levels of MDA, TNF-α, and ROS. Correspondingly, dapagliflozin reduced the expression of CX3CL1/CX3CR1, NF-κB p65 DNA binding activity, and it also attenuated nuclear acetylated NF-κB p65 in LPS-induced injury in H9c2 cells compared to untreated cells.

Conclusion: These findings shed light on the novel pharmacological potential of dapagliflozin in the alleviation of LPS-induced CX3CL1/CX3CR1-mediated injury in inflammatory conditions such as sepsis-induced cardiomyopathy.

Keywords: Dapagliflozin, fractalkine, CX3CL1/CX3CR1, NF-κB, H9c2 cells, lipopolysaccharide.

Graphical Abstract

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