ArticleMolecular medicine (Cambridge, Mass.)2022
Spermidine protects against acute kidney injury by modulating macrophage NLRP3 inflammasome activation and mitochondrial respiration in an eIF5A hypusination-related pathway.
Article in Molecular medicine (Cambridge, Mass.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 38 citations in OpenAlex.
- Lubiprostone in chronic kidney disease: Insights into mitochondrial function and polyamines from a randomized phase 2 clinical trial.Science advances · 2025Trial
- L-Arginine inhibits NLRP3 inflammasome activation.Nature metabolism · 2026Article
- Spermine suppressesmBio · 2026Article
- Article
- Spatial metabolomics: A new tool for unravelling the metabolic disorders and heterogeneity in diabetic kidney disease (Review).International journal of molecular medicine · 2026Review
- The role of spermidine in plants and humans: a pathway from climate change adaptation to health benefits.NPJ science of food · 2026Review
- Untangling amino acid metabolism in renal diseases: mechanisms, dysregulation, and critical gaps.Clinical kidney journal · 2026Review
- NLRP3 inflammasome in acute kidney injury: molecular mechanisms, post-translational regulation, and immunotherapeutic potential.Frontiers in immunology · 2026Review
- Gut microbial-derived metabolites: key players in kidney disease and renal fibrosis.International journal of biological sciences · 2026Review
- Ornithine decarboxylase influences granulosa cell proliferation and steroidogenesis: implications for ovarian regression in Wuding chickens.Frontiers in veterinary science · 2026Article
- Potential dietary geroprotectors and their impact on key mechanisms of aging.Biogerontology · 2025Review
- Transcription factor FOS promotes ferroptosis and inflammation in S. aureus- infected osteomyelitis via EIF5A.Journal of orthopaedic surgery and research · 2025Article
- Spermidine as a Potential Protective Agents Against Poly(I:C)-Induced Immune Response, Oxidative Stress, Apoptosis, and Testosterone Decrease in Yak Leydig Cells.International journal of molecular sciences · 2025Article
- Polyamine metabolism and anti-tumor immunity.Frontiers in immunology · 2025Review
- Acute kidney injury through a metabolic lens: pathological reprogramming mechanisms and clinical translation potential.Frontiers in physiology · 2025Review
- Anti-inflammatory effects of 1,7-dihydroxy-3,4-dimethoxyxanthone through inhibition of M1-phenotype macrophages via arginine/mitochondrial axis.Immunologic research · 2024Article
- Spermidine Associated with Gut Microbiota Protects Against MRSA Bloodstream Infection by Promoting Macrophage M2 Polarization.ACS infectious diseases · 2024Article
- Inflammation primes the murine kidney for recovery by activating AZIN1 adenosine-to-inosine editing.The Journal of clinical investigation · 2024Article
- Renal macrophages and NLRP3 inflammasomes in kidney diseases and therapeutics.Cell death discovery · 2024Review
- Polyamine Signal through HCC Microenvironment: A Key Regulator of Mitochondrial Preservation and Turnover in TAMs.International journal of molecular sciences · 2024Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAcute kidney injury (AKI) is still a critical problem in clinical practice, with a heavy burden for national health system around the world. It is notable that sepsis is the predominant cause of AKI for patients in the intensive care unit and the mortality remains considerably high. The treatment for AKI relies on supportive therapies and almost no specific treatment is currently available. Spermidine is a naturally occurring polyamine with pleiotropic effects. However, the renoprotective effect of spermidine and the underlying mechanism remain elusive.
methodsWe employed mice sepsis-induced AKI model and explored the potential renoprotective effect of spermidine in vivo with different administration time and routes. Macrophage depleting was utilized to probe the role of macrophage. In vitro experiments were conducted to examine the effect of spermidine on macrophage cytokine secretion, NLRP3 inflammasome activation and mitochondrial respiration.
resultsWe confirmed that spermidine improves AKI with different administration time and routes and that macrophages serves as an essential mediator in this protective effect. Meanwhile, spermidine downregulates NOD-like receptor protein 3 (NLRP3) inflammasome activation and IL-1 beta production in macrophages directly. Mechanically, spermidine enhances mitochondrial respiration capacity and maintains mitochondria function which contribute to the NLRP3 inhibition. Importantly, we showed that eukaryotic initiation factor 5A (eIF5A) hypusination plays an important role in regulating macrophage bioactivity.
conclusionsSpermidine administration practically protects against sepsis-induced AKI in mice and macrophages serve as an essential mediator in this protective effect. Our study identifies spermidine as a promising pharmacologic approach to prevent AKI.
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