Modulation of autophagy and PI3K/Akt/mTOR pathway by naringin in sepsis-induced acute kidney injury
IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES, cilt.29, sa.11, ss.1677-1687, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 29 Sayı: 11
- Basım Tarihi: 2026
- Doi Numarası: 10.22038/ijbms.2026.94607.20404
- Dergi Adı: IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, Index Islamicus, Directory of Open Access Journals, Academic Search Ultimate (EBSCO), Middle East & Africa Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest)
- Sayfa Sayıları: ss.1677-1687
- Erciyes Üniversitesi Adresli: Evet
Özet
Objective(s): Sepsis-induced acute kidney injury (SI-AKI) is a life-threatening complication with limited treatment options, contributing to high morbidity and mortality worldwide. This study explores the renoprotective effects of naringin (NRG), a bioactive flavonoid, in a rat model of SI-AKI. It hypothesizes that NRG mitigates renal damage by enhancing autophagy and modulating the PI3K/ Akt/mTOR pathway, thereby reducing oxidative stress, inflammation, and cellular injury. Materials and Methods: Rats were divided into Control, NRG, LPS, LPS+NRG, and LPS+NRG+3MA groups. NRG (100 mg/kg) was administered for 14 days, while LPS (10 mg/kg) induced sepsis. The LPS+NRG+3-MA group received 3-MA (30 mg/kg) to inhibit autophagy. Histopathological, immunohistochemical, gene expression, and biochemical analyses were performed. LPS-induced sepsis caused severe renal injury, including inflammation, tubular dilation, and oxidative stress (increased MDA, decreased catalase), alongside elevated TNF-alpha, NGAL, and KIM-1. Results: NRG treatment significantly preserved renal structure, reduced oxidative stress, and lowered TNF-alpha, NGAL, and KIM-1 levels. Immunohistochemistry showed increased Beclin-1 and LC3 expression in the LPS+NRG group, suggesting enhanced autophagy. Gene expression analysis revealed activation of the PI3K/Akt/mTOR pathway in NRG-treated rats. Conclusion: These findings indicate that NRG protects against SI-AKI by promoting autophagy and activating pro-survival pathways, offering a novel therapeutic strategy for sepsis management by regulating autophagy and modulating pathways.