ArticleJournal of clinical medicine2019
Indoxyl Sulfate Induces Apoptosis Through Oxidative Stress and Mitogen-Activated Protein Kinase Signaling Pathway Inhibition in Human Astrocytes.
Article in Journal of clinical medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 52 citations in OpenAlex.
- Lacticaseibacillus rhamnosus attenuates uremic toxins in patients with nondialysis chronic kidney disease through the anti-inflammatory molecules.Scientific reports · 2025Trial
- Targeting Uremic Toxins in Chronic Kidney Disease: Current Challenges and Emerging Therapeutic Strategies.Toxins · 2026Review
- The Kidney-Brain Axis in Chronic Kidney Disease: Uremic Toxins, Cognitive Decline, Mechanistic Pathways, Biomarkers and Therapeutic Perspectives.Biomedicines · 2026Review
- Dysfunction of cerebrospinal fluid circulation and neurovascular decoupling in end-stage renal disease patients with mild cognitive impairment.GeroScience · 2026Article
- Cerebral Neurodegeneration and Cognitive Impairment in Patients on Maintenance Hemodialysis: the Role of Neuroglia and Associated Factors (Review).Sovremennye tekhnologii v meditsine · 2026Review
- A nomogram for predicting ICU mortality of sepsis associated encephalopathy: a retrospective cohort study based on MIMIC-IV and eICU-CRD.BMC medical informatics and decision making · 2025Article
- Klotho: A multifaceted protector in sepsis-induced organ damage and a potential therapeutic target.World journal of critical care medicine · 2025Review
- Gamma-tocopherol vitamin E enhances the cytotoxicity of p-cresyl sulfate to renal tubular cells.European journal of medical research · 2025Article
- Research progress on the kidney-gut-brain axis in brain dysfunction in maintenance hemodialysis patients.Frontiers in medicine · 2025Review
- Cerebral white matter damage in patients with end-stage kidney disease associates with cognitive impairment.Clinical kidney journal · 2025Article
- The evolving understanding of systemic mechanisms in organ-specific IgA nephropathy: a focus on gut-kidney crosstalk.Theranostics · 2025Review
- Regulation of the blood-brain barrier function by peripheral cues in health and disease.Metabolic brain disease · 2024Review
- Indoxyl sulfate induces apoptotic cell death by inhibiting glycolysis in human astrocytes.Kidney research and clinical practice · 2024Article
- α-synuclein overexpression and the microbiome shape the gut and brain metabolome in mice.NPJ Parkinson's disease · 2024Article
- AST-120 Protects Cognitive and Emotional Impairment in Chronic Kidney Disease Induced by 5/6 Nephrectomy.Brain sciences · 2024Article
- α-Synuclein Overexpression and the Microbiome Shape the Gut and Brain Metabolome in Mice.bioRxiv : the preprint server for biology · 2024Article
- Uremic toxins and the brain in chronic kidney disease.Journal of nephrology · 2024Review
- Connecting the Dots: The Cerebral Lymphatic System as a Bridge Between the Central Nervous System and Peripheral System in Health and Disease.Aging and disease · 2024Review
- Emotional and cognitive changes in chronic kidney disease.The Korean journal of internal medicine · 2022Review
- Production of Indole and Indole-Related Compounds by the Intestinal Microbiota and Consequences for the Host: The Good, the Bad, and the Ugly.Microorganisms · 2022Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Uremic toxins accumulated in chronic kidney disease (CKD) increases the risk of cognitive impairment. Indoxyl sulfate (IS) is a well-known protein-bound uremic toxin that is correlated with several systemic diseases, but no studies on human brain cells are available. We investigated the effect of IS on primary human astrocytes through next-generation sequencing and cell experiment confirmation to explore the mechanism of IS-associated brain damage. Total RNAs extracted from IS-treated and control astrocytes were evaluated by performing functional and pathway enrichment analysis. The toxicities of IS in the astrocytes were investigated in terms of cell viability through flow cytometry; the signal pathway was then investigated through immunoblotting. IS stimulated the release of reactive oxygen species, increased nuclear factor (erythroid-derived 2)-like 2 levels, and reduced mitochondrial membrane potential. IS triggered astrocyte apoptosis by inhibiting the mitogen-activated protein kinase (MAPK) pathway, including extracellular-signal-regulated kinase (ERK), MAPK/ERK kinase, c-Jun N-terminal kinase, and p38. The decreased ERK phosphorylation was mediated by the upregulated dual-specificity phosphatase 1, 5, 8, and 16. In conclusion, IS can induce neurotoxicity in patients with CKD and the pathogenesis involves cell apoptosis through oxidative stress induction and MAPK pathway inhibition in human astrocytes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.