EMPAGLIFLOZIN MITIGATES ISCHEMIA/REPERFUSION-INDUCED LIVER INJURY IN RATS: MODULATION OF NF-ΚB, SMAD-4, VEGF, AND FIBRINOGEN PROTEIN EXPRESSIONS
Abouzed, D., Mahmoud, H., Murad, A., Hemada, R. (2024). EMPAGLIFLOZIN MITIGATES ISCHEMIA/REPERFUSION-INDUCED LIVER INJURY IN RATS: MODULATION OF NF-ΚB, SMAD-4, VEGF, AND FIBRINOGEN PROTEIN EXPRESSIONS. EKB Journal Management System, 47(1), 597-612. doi: 10.21608/bfsa.2023.240917.1944
DeiaaEldeen Elsayed Abouzed; Heba Mohsen Mahmoud; Amira Murad; Ramadan Hemada Hemada. "EMPAGLIFLOZIN MITIGATES ISCHEMIA/REPERFUSION-INDUCED LIVER INJURY IN RATS: MODULATION OF NF-ΚB, SMAD-4, VEGF, AND FIBRINOGEN PROTEIN EXPRESSIONS". EKB Journal Management System, 47, 1, 2024, 597-612. doi: 10.21608/bfsa.2023.240917.1944
Abouzed, D., Mahmoud, H., Murad, A., Hemada, R. (2024). 'EMPAGLIFLOZIN MITIGATES ISCHEMIA/REPERFUSION-INDUCED LIVER INJURY IN RATS: MODULATION OF NF-ΚB, SMAD-4, VEGF, AND FIBRINOGEN PROTEIN EXPRESSIONS', EKB Journal Management System, 47(1), pp. 597-612. doi: 10.21608/bfsa.2023.240917.1944
Abouzed, D., Mahmoud, H., Murad, A., Hemada, R. EMPAGLIFLOZIN MITIGATES ISCHEMIA/REPERFUSION-INDUCED LIVER INJURY IN RATS: MODULATION OF NF-ΚB, SMAD-4, VEGF, AND FIBRINOGEN PROTEIN EXPRESSIONS. EKB Journal Management System, 2024; 47(1): 597-612. doi: 10.21608/bfsa.2023.240917.1944

EMPAGLIFLOZIN MITIGATES ISCHEMIA/REPERFUSION-INDUCED LIVER INJURY IN RATS: MODULATION OF NF-ΚB, SMAD-4, VEGF, AND FIBRINOGEN PROTEIN EXPRESSIONS

Bulletin of Pharmaceutical Sciences Assiut University
Article 40, Volume 47, Issue 1, June 2024, Page 597-612  XML PDF (1.65 MB)
Document Type: Original Article
DOI: 10.21608/bfsa.2023.240917.1944
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Authors
DeiaaEldeen Elsayed Abouzed email 1; Heba Mohsen Mahmoud2; Amira Murad2; Ramadan Hemada Hemada3
1Department of Pharmacology, Faculty of pharmacy, Sohag University
2Department of Pharmacology, Faculty of Pharmacy, Beni Suef University
3Department of Pharmacology-Faculty of pharmacy-Deraya University
Abstract
Liver ischemia/reperfusion (IR) injury is a critical cause of mortality in patients undergoing liver transplantation. Our objective was to assess the protective impact of empagliflozin (EGZ) on IR-induced liver damage in rats and to investigate its potential protective mechanism. A total of 24 male Wistar albino rats were randomly divided into four groups: sham; IR; EGZ (10 mg/kg/day; p.o) and IR + EGZ. Serum levels of aminotransferase ALT and AST, gamma glutamyl transferase GGT and total bilirubin TB were evaluated. Liver samples were used to evaluate oxidative stress indicators, reduced glutathione GSH, malondialdehyde MDA, total nitic oxide NOx and myeloperoxidase MPO, inflammatory mediators as tumor necrosis factor alpha TNF-α and interleukin -33 IL-33, and apoptosis markers, Bcl-2-associated X protein Bax, galactine-9 Gal9 and B-cell lymphoma 2 Bcl2. Hepatic vascular endothelial growth factor VEGF and fibrinogen expressions were determined by Western blot analysis. Immunohistochemical analysis for hepatic SMAD-4 and NF-κB was performed along with histopathological examination. Pretreatment with EGZ significantly ameliorated liver functions and oxidative stress compared to IR injury model. Similarly, the inflammatory cytokines were significantly decreased along with marked decline of the apoptosis biomarkers and a significant decrease of VEGF and fibrinogen expressions. Additionally, SMAD-4 and NF-κB protein expressions were significantly decreased compared to IR group. These results were further supported by improvement liver architecture. Our findings suggested that EGZ has the potentiality to be protective against hepatic IRI.
Keywords
Empagliflozin; Fibrinogen; Ischemia reperfusion; Liver; SMAD-4 and VEGF
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