Title:Dapagliflozin Protects H9c2 Cells Against Injury Induced by
Lipopolysaccharide via Suppression of CX3CL1/CX3CR1 Axis and NF-κB
Activity
Volume: 15
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*
Affiliation:
- Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Keywords:
Dapagliflozin, fractalkine, CX3CL1/CX3CR1, NF-κB, H9c2 cells, lipopolysaccharide.
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.
