Gastroprotective effect of dapagliflozin in ethanol-induced gastric lesions in rats: Crosstalk between HMGB1/RAGE/PTX3 and TLR4/MyD88/VEGF/PDGF signaling pathways.

Autor: Salama RM; Pharmacology and Toxicology Department, Faculty of Pharmacy, Misr International University (MIU), Cairo, Egypt. Electronic address: rania.salama@miuegypt.edu.eg., Ahmed RH; Faculty of Pharmacy, Misr International University (MIU), Cairo, Egypt. Electronic address: rodaina1709342@miuegypt.edu.eg., Farid AA; Faculty of Pharmacy, Misr International University (MIU), Cairo, Egypt. Electronic address: alaa1711259@miuegypt.edu.eg., AbdElSattar BA; Faculty of Pharmacy, Misr International University (MIU), Cairo, Egypt. Electronic address: basma1704215@miuegypt.edu.eg., AbdelBaset RM; Faculty of Pharmacy, Misr International University (MIU), Cairo, Egypt. Electronic address: radwa1710156@miuegypt.edu.eg., Youssef ME; Faculty of Pharmacy, Misr International University (MIU), Cairo, Egypt. Electronic address: mirna1703942@miuegypt.edu.eg., El Wakeel SA; Pharmacology and Toxicology Department, Faculty of Pharmacy, Misr International University (MIU), Cairo, Egypt. Electronic address: sara.abdulmeguid@miuegypt.edu.eg.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2023 Feb; Vol. 115, pp. 109686. Date of Electronic Publication: 2023 Jan 07.
DOI: 10.1016/j.intimp.2023.109686
Abstrakt: Alcohol abuse may lead to the development of gastric mucosal lesions. Dapagliflozin (DAPA), a sodium-glucose cotransporter-2 inhibitor, is clinically used to treat type 2 diabetes mellitus. However, studies showed protective effect of DAPA under various experimental conditions by alleviating oxidative stress and inflammation. The effect of DAPA on experimental gastric ulcer has not been studied yet. Therefore, we attempted to investigate DAPA's protective effect against ethanol (EtOH)-induced gastric lesions. Fifty-six (8-week-old) male Wistar rats were divided into seven groups. DAPA (1, 5, and 10 mg/kg/day; p.o.) was given for seven days, plus a single dose of absolute EtOH (5 ml/kg) on day 8. According to hematoxylin and eosin, and Alcian blue staining of gastric tissue sections, titratable acidity, and macroscopic assessments, DAPA high dose (10 mg/kg) was the most protective, with lesser ulcerations, and higher mucin, relative to the lower two doses and the standard treatment omeprazole (OME). In rats pre-treated with DAPA high dose, colorimetric and ELISA analyses revealed significantly decreased oxidative stress, pro-inflammatory, and apoptosis indices and increased levels of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). Western blot analysis revealed reduced pentraxin-3 (PTX3), high-mobility group box 1 (HMGB1), receptor for advanced glycation end products (RAGE), toll-like receptor 4 (TLR4), and myeloid differentiation factor 88 (MyD88) expression. These results were comparable in DAPA (10 mg/kg) and OME pre-treated groups. Overall, DAPA exerted a dose-dependent protective effect against EtOH-induced gastric injury. Gastroprotective effects of DAPA (10 mg/kg) may be associated with influencing HMGB1/RAGE/PTX3 and TLR4/MyD88/VEGF/PDGF pathways.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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