Iranian journal of basic medical sciences · 2026
Modulation of autophagy and PI3K/Akt/mTOR pathway by naringin in sepsis-induced acute kidney injury.
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Akin Ali Tugrul, Yilmaz Zeynep, Kaymak Emin, Varinli Şaban, Onal Esra, Deger Necla, Sayan Meryem, Karabulut Derya, Doganyigit Zuleyha, Toluk Ayse
Аннотация
OBJECTIVES: 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+3-MA 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-α, NGAL, and KIM-1.
RESULTS: NRG treatment significantly preserved renal structure, reduced oxidative stress, and lowered TNF-α, 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.
MATERIALS AND METHODS: Rats were divided into Control, NRG, LPS, LPS+NRG, and LPS+NRG+3-MA 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-α, NGAL, and KIM-1.
RESULTS: NRG treatment significantly preserved renal structure, reduced oxidative stress, and lowered TNF-α, 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.