Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

Modulation of autophagy and PI3K/Akt/mTOR pathway by naringin in sepsis-induced acute kidney injury

Articles in Press

Document Type : Original Article

Authors
Ali Tuğrul Akin 1, 2
Zeynep Yilmaz 3
Emin Kaymak 4
Saban Varinli 5
Esra Onal 6
Necla Deger 6
Meryem Sayan 6
Derya Karabulut 7
Zuleyha Doganyigit 4
Ayse Tuğrul Toluk 8
1 Istinye University, Faculty of Medicine, Department of Medical Biology, Istanbul, Turkey
2 King’s College London, Cancer and Pharmaceutical Sciences, The Rayne Institute, London, UK
3 Erciyes University, Genome and Stem Cell Center, Kayseri, Turkey
4 Yozgat Bozok University, Faculty of Medicine, Histology-Embryology Department, Yozgat, Turkey
5 Yozgat Bozok University, Graduate School of Health Sciences, Histology-Embryology Department, Yozgat, Turkey
6 Erciyes University, Graduate School of Health Sciences, Histology-Embryology Department, Kayseri, Turkey
7 Erciyes University, Faculty of Medicine, Histology-Embryology Department, Kayseri, Turkey
8 Erciyes University, Faculty of Science, Department of Biology, Kayseri, Turkey
10.22038/ijbms.2026.94607.20404
Abstract
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+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.
Keywords
Acute kidney injury
Autophagy
Inflammation
Naringin
Sepsis
Subjects
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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 22 September 2026