Sivelestat sodium protects against renal ischemia/reperfusion injury by reduction of NETs formation

IF 3.8 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Archives of biochemistry and biophysics Pub Date : 2025-01-23 DOI:10.1016/j.abb.2025.110318

Yanqi Liu , Yu Xin , Mengyao Yuan , Yuhan Liu , Yuchen Song , Lifeng Shen , Yu Xiao , Xinran Wang , Dawei Wang , Linqiong Liu , Yuxi Liu , Yinghao Luo , Pengfei Huang , Qianqian Zhang , Weiting Zhang , Hongxu Li , Yuxin Zhou , Xibo Wang , Kaijiang Yu , Changsong Wang

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引用次数: 0

Abstract

Background

Ischemia-reperfusion injury (IRI) often results in renal impairment. While the presence of neutrophil extracellular traps (NETs) is consistently observed, their specific impact on IRI is not yet defined. Sivelestat sodium, an inhibitor of neutrophil elastase which is crucial for NET formation, may offer a therapeutic approach to renal IRI, warranting further research.

Methods

A mouse model was established for early-stage renal IRI, confirmed by injury markers and histological assessments. The involvement of NETs in renal I/R was demonstrated using immunofluorescence and Western blot. Renal function and pathology were further evaluated through a comprehensive set of methods, including Periodic Acid-Schiff staining (PAS) and Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) staining, enzyme-linked immunosorbent assay (ELISA), Real time Glomerular Filtration Rate (RT-GFR) monitoring, Polymerase Chain Reaction (PCR), biochemical analysis, and additional Western blot and immunofluorescence assays.

Results

We firstly quantified NET expression in renal IRI mice, noting a peak at 24 h. Subsequently, sivelestat sodium treatment was administered, resulting in decreased MPO, CitH3, and attenuated tubular damage. Moreover, it resulted in a decrease in serum levels of creatinine, blood urea nitrogen (BUN), as well as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). Additionally, it lowered the abundance of renal tissue inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and mitigated the levels of oxidative stress indicators malondialdehyde (MDA) and 4 Hydroxynonenal (4HNE), accompanied by a decline in renal cell apoptosis and an enhancement of GFR in renal I/R mice.

Conclusion

Sivelestat sodium ameliorates renal IRI by downregulating neutrophil NETs, reducing inflammation, oxidative stress, and apoptosis, thereby enhancing renal function.

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来源期刊

Archives of biochemistry and biophysics 生物-生化与分子生物学

CiteScore

7.40

自引率

0.00%

发文量

245

审稿时长

26 days

期刊介绍： Archives of Biochemistry and Biophysics publishes quality original articles and reviews in the developing areas of biochemistry and biophysics. Research Areas Include: • Enzyme and protein structure, function, regulation. Folding, turnover, and post-translational processing • Biological oxidations, free radical reactions, redox signaling, oxygenases, P450 reactions • Signal transduction, receptors, membrane transport, intracellular signals. Cellular and integrated metabolism.