Empagliflozin protects against indomethacin-induced gastric injury in rats: evidence from inflammatory, apoptotic, and early PI3K/Akt/VEGF-related changes
INFLAMMOPHARMACOLOGY, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Basım Tarihi: 2026
- Doi Numarası: 10.1007/s10787-026-02374-4
- Dergi Adı: INFLAMMOPHARMACOLOGY
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE, Academic Search Ultimate (EBSCO), Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Health Research Premium Collection (ProQuest)
- Recep Tayyip Erdoğan Üniversitesi Adresli: Evet
Özet
Non-steroidal anti-inflammatory drugs (NSAIDs), particularly indomethacin, are widely used for the treatment of pain and inflammation but frequently cause gastric mucosal injury. Empagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor primarily used for type 2 diabetes, has recently attracted attention due to its anti-inflammatory, antioxidant, and cytoprotective properties. The present study investigated the potential gastroprotective effects of empagliflozin against indomethacin-induced gastric injury in rats and explored the underlying mechanisms related to inflammation, oxidative stress, apoptosis, and PI3K/Akt/VEGF-related signaling pathways. Male Sprague-Dawley rats were divided into six groups: control, indomethacin, indomethacin + famotidine, indomethacin + empagliflozin (10 mg/kg), indomethacin + empagliflozin (20 mg/kg), and empagliflozin (20 mg/kg). Rats were pretreated with empagliflozin for 7 days before induction of acute gastric injury with indomethacin. Gastric tissues were evaluated using biochemical, histopathological, immunohistochemical, and Western blot analyses. Indomethacin administration significantly increased pro-inflammatory cytokines (TNF-alpha and IL-6), reduced prostaglandin E2 levels, and increased cleaved caspase-3 expression, indicating activation of inflammatory and apoptotic pathways. Empagliflozin treatment significantly reduced inflammatory cytokine levels, restored prostaglandin levels, and suppressed cleaved caspase-3 expression, while oxidative stress-related parameters showed limited and non-uniform changes. In addition, empagliflozin was associated with changes in cyclooxygenase activity and PI3K/Akt/VEGF-related signaling in this acute injury model. Histopathological findings were generally consistent with the biochemical results and suggested partial improvement in gastric mucosal damage following empagliflozin treatment. Taken together, these findings indicate that empagliflozin exerts gastroprotective effects mainly through modulation of inflammatory and apoptotic pathways, with accompanying early changes in oxidative stress-related parameters and PI3K/Akt/VEGF-related signaling. These results suggest that empagliflozin may represent a potential candidate for the prevention of NSAID-induced gastric injury.