ArticleFrontiers in immunology2021
Kynurenic Acid and Its Synthetic Derivatives Protect Against Sepsis-Associated Neutrophil Activation and Brain Mitochondrial Dysfunction in Rats.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Research Advances in the Pathogenesis of Sepsis-Associated Encephalopathy.International journal of molecular sciences · 2026Review
- Probiotics-enhanced kynurenic acid mitigates cisplatin-induced nephrotoxicity in mice.iScience · 2026Article
- From Polyphenols to Prodrugs: Bridging the Blood-Brain Barrier with Nanomedicine and Neurotherapeutics.International journal of molecular sciences · 2026Review
- Extracellular Histones Associate with Blood-Brain Barrier Disruption and Astrocyte-Mediated Neuroinflammation During Polymicrobial Sepsis.International journal of molecular sciences · 2026Article
- Receptor-Mitochondria Crosstalk in the Kynurenine Metabolic Pathway: Integrating Metabolomics and Clinical Mass Spectrometry.Antioxidants (Basel, Switzerland) · 2026Review
- Fumarate inhibits the formation of neutrophil extracellular traps (NETs) in a Nrf2-controlled and Annexin-A1-dependent manner associated with mitochondrial fusion.Frontiers in immunology · 2026Article
- Kynurenic Acid Protects Against Myocardial Ischemia/Reperfusion Injury by Activating GPR35 Receptors and Preserving Mitochondrial Structure and Function.Biomolecules · 2025Article
- A citrullinated histone H3 monoclonal antibody for immune modulation in sepsis.Nature communications · 2025Article
- The Pharmacological Evidences for the Involvement of AhR and GPR35 Receptors in Kynurenic Acid-Mediated Cytokine and Chemokine Secretion by THP-1-Derived Macrophages.Molecules (Basel, Switzerland) · 2025Article
- The Power Struggle: Kynurenine Pathway Enzyme Knockouts and Brain Mitochondrial Respiration.Journal of neurochemistry · 2025Article
- Quinoline Quest: Kynurenic Acid Strategies for Next-Generation Therapeutics via Rational Drug Design.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Increased cell-free DNA in CSF and serum of hip fracture patients with delirium.Brain communications · 2025Article
- Identification and Evaluation of Lipocalin-2 in Sepsis-Associated Encephalopathy via Machine Learning Approaches.Journal of inflammation research · 2025Article
- Gut microbiota and sepsis-associated encephalopathy: pathogenesis and precision therapies.Frontiers in neuroscience · 2025Review
- Revolutionizing our understanding of Parkinson's disease: Dr. Heinz Reichmann's pioneering research and future research direction.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- The Biology and Biochemistry of Kynurenic Acid, a Potential Nutraceutical with Multiple Biological Effects.International journal of molecular sciences · 2024Review
- Role of Kynurenine and Its Derivatives in the Neuroimmune System.International journal of molecular sciences · 2024Review
- The Impact of C-3 Side Chain Modifications on Kynurenic Acid: A Behavioral Analysis of Its Analogs in the Motor Domain.International journal of molecular sciences · 2024Article
- Gut Microbiota in Ischemic Stroke: Role of Gut Bacteria-Derived Metabolites.Translational stroke research · 2023Review
- Differential Effects of Hypothermia and SZR72 on Cerebral Kynurenine and Kynurenic Acid in a Piglet Model of Hypoxic-Ischemic Encephalopathy.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
17 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background and Aims: The systemic host response in sepsis is frequently accompanied by central nervous system (CNS) dysfunction. Evidence suggests that excessive formation of neutrophil extracellular traps (NETs) can increase the permeability of the blood-brain barrier (BBB) and that the evolving mitochondrial damage may contribute to the pathogenesis of sepsis-associated encephalopathy. Kynurenic acid (KYNA), a metabolite of tryptophan catabolism, exerts pleiotropic cell-protective effects under pro-inflammatory conditions. Our aim was to investigate whether exogenous KYNA or its synthetic analogues SZR-72 and SZR-104 affect BBB permeability secondary to NET formation and influence cerebral mitochondrial disturbances in a clinically relevant rodent model of intraabdominal sepsis. Methods: Sprague-Dawley rats were subjected to fecal peritonitis (0.6 g kg Results: Sepsis was characterized by significantly elevated ROFA scores, while the increased BBB permeability and plasma S100B levels demonstrated brain damage. Plasma levels of CitH3, MPO and IL-1β were elevated in sepsis but were ameliorated by KYNA and its synthetic analogues. The sepsis-induced deterioration in tissue CI-CII-linked OXPHOS and BBB parameters as well as the increase in tissue MPO content were positively affected by KYNA/KYNA analogues. Conclusion: This study is the first to report that KYNA and KYNA analogues are potential neuroprotective agents in experimental sepsis. The proposed mechanistic steps involve reduced peripheral NET formation, lowered BBB permeability changes and alleviation of mitochondrial dysfunction in the CNS.
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