ArticleThe American journal of pathology2015
Valproic Acid Limits Pancreatic Recovery after Pancreatitis by Inhibiting Histone Deacetylases and Preventing Acinar Redifferentiation Programs.
Article in The American journal of pathology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
17 citing papers in PubMed, 35 citations in OpenAlex.
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- Valproic Acid-Induced Pancreatitis in a Pediatric Patient With 17q12 Duplication Syndrome.Cureus · 2026Article
- Moringa Oleifera mitigates oxidative stress and pancreatic toxicity induced by sodium valproate in female Sprague Dawley rats.Journal of molecular histology · 2025Article
- The Role of the Gut Microbiome in the Development of Acute Pancreatitis.International journal of molecular sciences · 2024Review
- Epigenetic small-molecule screen for inhibition and reversal of acinar ductal metaplasia in mouse pancreatic organoids.Frontiers in pharmacology · 2024Article
- Acinar-to-Ductal Metaplasia (ADM): On the Road to Pancreatic Intraepithelial Neoplasia (PanIN) and Pancreatic Cancer.International journal of molecular sciences · 2023Review
- The Role of Endoplasmic Reticulum Stress in Cell Injury Induced by Methimazole on Pancreatic Cells.Advanced pharmaceutical bulletin · 2023Article
- Urolithin A attenuates severity of chronic pancreatitis associated with continued alcohol intake by inhibiting PI3K/AKT/mTOR signaling.American journal of physiology. Gastrointestinal and liver physiology · 2022Article
- Pancreas and Adverse Drug Reactions: A Literature Review.Drug safety · 2022Review
- A Practical Approach to Management of Acute Pancreatitis: Similarities and Dissimilarities of Disease in Children and Adults.Journal of clinical medicine · 2021Review
- Epigenetic Effects Mediated by Antiepileptic Drugs and their Potential Application.Current neuropharmacology · 2020Review
- Pancreatitis in Children.Gastroenterology · 2019Review
- Valproic acid induced necrohemorragic pancreatitis: Case report and diagnostic approach in uncommon pancreatitis.International journal of surgery case reports · 2019Article
- Pancreatic gene expression during recovery after pancreatitis reveals unique transcriptome profiles.Scientific reports · 2018Article
- Class I histone deacetylase inhibition improves pancreatitis outcome by limiting leukocyte recruitment and acinar-to-ductal metaplasia.British journal of pharmacology · 2017Article
- A supervised learning framework for pancreatic islet segmentation with multi-scale color-texture features and rolling guidance filters.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2016Article
- The effect of long-term valproic acid treatment in the level of total cholesterol among adult.Indian journal of pharmacologyArticle
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
The mechanisms by which drugs induce pancreatitis are unknown. A definite cause of pancreatitis is due to the antiepileptic drug valproic acid (VPA). On the basis of three crucial observations-that VPA inhibits histone deacetylases (HDACs), HDACs mediate pancreas development, and aspects of pancreas development are recapitulated during recovery of the pancreas after injury-we hypothesized that VPA does not cause injury on its own, but it predisposes patients to pancreatitis by inhibiting HDACs and provoking an imbalance in pancreatic recovery. In an experimental model of pancreatic injury, we found that VPA delayed recovery of the pancreas and reduced acinar cell proliferation. In addition, pancreatic expression of class I HDACs (which are the primary VPA targets) increased in the midphase of pancreatic recovery. VPA administration inhibited pancreatic HDAC activity and led to the persistence of acinar-to-ductal metaplastic complexes, with prolonged Sox9 expression and sustained β-catenin nuclear activation, findings that characterize a delay in regenerative reprogramming. These effects were not observed with valpromide, an analog of VPA that lacks HDAC inhibition. This is the first report, to our knowledge, that VPA shifts the balance toward pancreatic injury and pancreatitis through HDAC inhibition. The work also identifies a new paradigm for therapies that could exploit epigenetic reprogramming to enhance pancreatic recovery and disorders of pancreatic injury.
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Registered trials
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.