Dapagliflozin Protection against Myocardial Ischemia by Modulating Sodium-glucose Transporter 2 Inhibitor, Silent Information Regulator 1, and Fatty Acid Synthase Expressions

Eman Sweed; Dina Sweed; Nader Galal; Huda Ibrahim Abd-Elhafiz

doi:10.3889/oamjms.2022.10861

Authors

Eman Sweed Department of Clinical Pharmacology, Faculty of Medicine, Menoufia University, Shebin Elkom, Menoufia, Egypt https://orcid.org/0000-0003-3689-2648
Dina Sweed Department of Pathology, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia, Egypt
Nader Galal Department of Anatomy and Embryology, Faculty of Medicine, Menoufia University, Shebin Elkom, Menoufia, Egypt https://orcid.org/0000-0001-5424-3268
Huda Ibrahim Abd-Elhafiz Department of Clinical Pharmacology, Faculty of Medicine, Menoufia University, Shebin Elkom, Menoufia, Egypt https://orcid.org/0000-0003-0958-8683

DOI:

https://doi.org/10.3889/oamjms.2022.10861

Keywords:

Dapagliflozin, FASN, Ischemic myocardium, Isoproterenol, SGLT2, SIRT1

Abstract

BACKGROUND: The emerging role of sodium-glucose transporter 2 (SGLT2) inhibitors drugs as potential therapeutic agents in myocardial ischemic (MI) injury treatment has raised the concern for possible mechanisms of action.

AIM: The current experimental study aimed to investigate the possible protective effects of dapagliflozin (DAPA) a SGLT2i, on isoproterenol (ISO)-induced MI in rats.

MATERIALS AND METHODS: Thirty Wistar rats were divided randomly and equally into three groups. Group 1 (control group): Received 1.0 mL of normal saline through an orogastric tube for 14 days. Group 2 (ISO group): Received 1.0 mL of normal saline orally through an orogastric tube for 14 days. In the last 2 days (days 13 and 14), ISO (100 mg/kg) was freshly dissolved in normal saline and injected subcutaneously once daily. Group 3 (ISO + DAPA-treated group): Received DAPA 1.0 mg/kg/day orally for 14 days. In the last 2 days (days 13 and 14), ISO (100 mg/kg) was introduced like that described in Group 2.

RESULTS: DAPA protects MI development by reversal of blood pressure changes, electrocardiographic alterations, stabilization of cardiac enzymes, inflammation restoration, oxidative stress, and lipid profile. SGLT2 was overexpressed in the ISO-induced MI, which declined in the ISO + DAPA group. Moreover, DAPA induced silent information regulator 1 (SIRT1)/fatty acid synthase (FASN) overexpression in ISO-induced MI. DAPA could have a potential protective role against acute MI.

CONCLUSION: DAPA protects against acute MI by modulating SIRT1 and FASN expression in cardiac muscles, suppressing oxidative stress, and downregulating inflammatory mediators.

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