ArticleThe American journal of pathology2016
Ketamine-Induced Apoptosis in Normal Human Urothelial Cells: A Direct, N-Methyl-d-Aspartate Receptor-Independent Pathway Characterized by Mitochondrial Stress.
Article in The American journal of pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 63 citations in OpenAlex.
- Ketamine uropathy: an update on pathophysiology, complications, and treatment options.The Canadian journal of urology · 2026Review
- Mitochondrial damage causes inflammation via cGAS-STING signaling in ketamine-induced cystitis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Hemorrhagic cystitis induced by intravenous esketamine in the treatment of new-onset refractory status epilepticus in children: a case report.Frontiers in pediatrics · 2025Article
- Ketamine-associated upper urinary tract dysfunction: What we know from current literature.Asian journal of urology · 2025Review
- A General Picture of Cucurbit[8]uril Host-Guest Binding: Recalibrating Bonded Interactions.Molecules (Basel, Switzerland) · 2023Article
- Ketamine promotes breast tumor growth in a mouse breast tumor model involving with high expression of miR-27b-3p and EGFR.Investigational new drugs · 2022Article
- LPCAT4 Knockdown Alters Barrier Integrity and Cellular Bioenergetics in Human Urothelium.International journal of molecular sciences · 2022Article
- Norketamine, the Main Metabolite of Ketamine, Induces Mitochondria-Dependent and ER Stress-Triggered Apoptotic Death in Urothelial Cells via a CaInternational journal of molecular sciences · 2022Article
- Molecular Pathophysiology and Potential Therapeutic Strategies of Ketamine-Related Cystitis.Biology · 2022Review
- Beyond the Raskin Protocol: Ketamine, Lidocaine, and Other Therapies for Refractory Chronic Migraine.Current pain and headache reports · 2021Review
- Prevention and Management of Common Adverse Effects of Ketamine and Esketamine in Patients with Mood Disorders.CNS drugs · 2021Review
- Association of urinary ketamine and APOA1 levels with bladder dysfunction in ketamine abusers revealed via proteomics and targeted metabolite analyses.Scientific reports · 2021Article
- Ketamine-induced urological toxicity: potential mechanisms and translation for adults with mood disorders receiving ketamine treatment.Psychopharmacology · 2021Review
- Smaller bladder capacity and stronger bladder contractility in patients with ketamine cystitis are associated with elevated TRPV1 and TRPV4.Scientific reports · 2021Article
- Neuron-Glia Crosstalk Plays a Major Role in the Neurotoxic Effects of KetamineFrontiers in cell and developmental biology · 2021Article
- Urothelial toxicity of esketamine in the treatment of depression.Psychopharmacology · 2020Article
- Suppression of mIFrontiers in pharmacology · 2020Article
- Uncoupling DAPK1 from NMDA receptor GluN2B subunit exerts rapid antidepressant-like effects.Molecular psychiatry · 2018Article
- Article
- Urinary metabonomics of rats with ketamine-induced cystitis using GC-MS spectroscopy.International journal of clinical and experimental pathology · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Recreational abuse of ketamine has been associated with the emergence of a new bladder pain syndrome, ketamine-induced cystitis, characterized by chronic inflammation and urothelial ulceration. We investigated the direct effects of ketamine on normal human urothelium maintained in organ culture or as finite cell lines in vitro. Exposure of urothelium to ketamine resulted in apoptosis, with cytochrome c release from mitochondria and significant subsequent caspase 9 and 3/7 activation. The anesthetic mode-of-action for ketamine is mediated primarily through N-methyl d-aspartate receptor (NMDAR) antagonism; however, normal (nonimmortalized) human urothelial cells were unresponsive to NMDAR agonists or antagonists, and no expression of NMDAR transcript was detected. Exposure to noncytotoxic concentrations of ketamine (≤1 mmol/L) induced rapid release of ATP, which activated purinergic P2Y receptors and stimulated the inositol trisphosphate receptor to provoke transient release of calcium from the endoplasmic reticulum into the cytosol. Ketamine concentrations >1 mmol/L were cytotoxic and provoked a larger-amplitude increase in cytosolic Ca(2+) concentration that was unresolved. The sustained elevation in cytosolic Ca(2+) concentration was associated with pathological mitochondrial oxygen consumption and ATP deficiency. Damage to the urinary barrier initiates bladder pain and, in ketamine-induced cystitis, loss of urothelium from large areas of the bladder wall is a reported feature. This study offers first evidence for a mechanism of direct toxicity of ketamine to urothelial cells by activating the intrinsic apoptotic pathway.
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