Effect of dapagliflozin on sepsis-induced kidney injury in a rat model: modulation of the NLRP3 pathway
Immunopharmacology and Immunotoxicology, cilt.47, sa.4, ss.533-540, 2025 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 47 Sayı: 4
- Basım Tarihi: 2025
- Doi Numarası: 10.1080/08923973.2025.2519597
- Dergi Adı: Immunopharmacology and Immunotoxicology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database
- Sayfa Sayıları: ss.533-540
- Anahtar Kelimeler: apoptosis, dapagliflozin, nephroprotection, NLRP3 inflammasome, Sepsis
- Süleyman Demirel Üniversitesi Adresli: Evet
Özet
Introduction: Sepsis-induced acute kidney injury (AKI) is a major cause of mortality in critically ill patients. Inflammation, oxidative stress, and apoptosis are key contributors to sepsis-related renal damage. Dapagliflozin (DPG), an SGLT2 inhibitor, has demonstrated anti-inflammatory and nephroprotective effects. This study aimed to investigate the renoprotective effects of DPG in a lipopolysaccharide (LPS)-induced sepsis model, focusing on inflammation, oxidative stress, and apoptosis in the kidneys. Methods: Thirty-two male Wistar albino rats were divided into four equal groups: (1) Control group, which received saline for 5 days; (2) LPS group, which received oral saline for 5 days and a single intraperitoneal LPS injection (5 mg/kg on day 5); (3) LPS+DPG group, which received oral DPG (10 mg/kg/day) for 5 days and a single intraperitoneal LPS injection (5 mg/kg on day 5); (4) DPG group, which received oral DPG (10 mg/kg/day) for 5 days. At the end of the experiment, samples were collected for histopathological, immunohistochemical, biochemical, and genetic analyses. Results: DPG significantly reduced serum urea and creatinine levels, indicating improved renal function. Histopathological analysis of the kidney tissues revealed reduced inflammation, hemorrhage, and necrosis in the LPS+DPG group compared to the LPS group. Also, DPG lowered the expression of pro-inflammatory markers (APAF-1, TNF-α, VCAM-1), reduced oxidative stress (decreased OSI), and downregulated NLRP3, caspase-1, IL-1β, and IL-18 gene expression. Conclusion: Prophylactic DPG administration exerts notable renoprotective effects in sepsis-induced AKI by mitigating inflammation, oxidative stress, and apoptosis. These findings highlight its potential as a preventive strategy, warranting further investigation in therapeutic contexts.