ArticleJournal of gastroenterology2013
Inhibition of lysosomal enzyme activities by proton pump inhibitors.
Article in Journal of gastroenterology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
What it found
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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
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Proton pump inhibitors and risk of liver cancer and mortality in patients with chronic liver disease: a systematic review and meta-analysis.European journal of clinical pharmacology · 2020Pooled it
- Sustained proton-pump inhibitor exposure and incident age-related macular degeneration: a new-user, population-based cohort study.BMJ open ophthalmology · 2026Observational
- Impact of proton pump inhibitors on immunotherapy is modulated by prior chemotherapy and linked to gut microbiome-immune cell signatures.Cancer immunology, immunotherapy : CII · 2026Article
- Association Between Proton Pump Inhibitor Use and Short-Term Postoperative Complications Following Abdominoplasty: A Multi-Institutional Cohort Study.Aesthetic surgery journal. Open forum · 2026Article
- Long-Term Use of Proton Pump Inhibitors Disrupts Intestinal Tight Junction Barrier and Exaggerates Experimental Colitis.Journal of Crohn's & colitis · 2023Article
- Ion Channel Drugs Suppress Cancer Phenotype in NG108-15 and U87 Cells: Toward Novel Electroceuticals for Glioblastoma.Cancers · 2022Article
- Chaperone-Mediated Autophagy of eNOS in Myocardial Ischemia-Reperfusion Injury.Circulation research · 2021Article
- Proton-pump inhibitors are associated with increased risk of prosthetic joint infection in patients with total hip arthroplasty: a case-cohort study.Acta orthopaedica · 2021Article
- Use of proton pump inhibitors in dialysis patients: a double-edged sword?Journal of nephrology · 2021Review
- Might proton pump or sodium-hydrogen exchanger inhibitors be of value to ameliorate SARs-CoV-2 pathophysiology?Physiological reports · 2021Review
- Macrolide antibiotics enhance the antitumor effect of lansoprazole resulting in lysosomal membrane permeabilization‑associated cell death.International journal of oncology · 2020Article
- No association between proton pump inhibitor use and ALS risk: a nationwide nested case-control study.Scientific reports · 2020Article
- Proton Pump Inhibitors in Children: the Good, the Bad, and the Ugly.Current allergy and asthma reports · 2020Review
- Bacterial Infection in Patients with Cirrhosis: Don't Get Bugged to Death.Digestive diseases and sciences · 2020Review
- Pharmacological Effects and Toxicogenetic Impacts of Omeprazole: Genomic Instability and Cancer.Oxidative medicine and cellular longevity · 2020Review
- Regulating Interactions Between Targeted Nanocarriers and Mononuclear Phagocyte System via an Esomeprazole-Based Preconditioning Strategy.International journal of nanomedicine · 2020Article
- In silico design of novel proton-pump inhibitors with reduced adverse effects.Frontiers of medicine · 2019Article
- Cellular uptake, intracellular distribution and degradation of Her2-targeting silk nanospheres.International journal of nanomedicine · 2019Article
- Proton pump inhibitor use and cancer mortality.International journal of cancer · 2018Article
- Association between Proton Pump Inhibitor Use and CNS Infection Risk: A Retrospective Cohort Study.Journal of clinical medicine · 2018Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundProton pump inhibitors (PPIs) are pro-drugs requiring an acidic pH for activation. The specificity of PPI toward the proton pump is mainly due to the extremely low pH at the parietal cell canalicular membrane where the pump is located. Reactivity of PPIs was also observed in moderately acidic environments like the renal collecting duct. But no PPI effect on lysosomal enzymes has been observed possibly because the previous studies were performed with liver tissue, where PPIs are metabolized.
methodsThe reactivity of PPIs (omeprazole, lansoprazole and pantoprazole) with a cysteine-containing peptide was analyzed by mass spectrometry, and the impact of PPIs on lysosomal enzymes was evaluated in cultured cells and mice. The effect of PPIs on the immune system was examined with a mouse tumor immunotherapy model.
resultsIncubation of a cysteine-containing peptide with PPIs at pH5 led to the conversion of most of the peptide into PPI-peptide adducts. Dose dependent inhibition of lysosomal enzyme activities by PPIs was observed in cultured cells and mouse spleen. Further, PPI counteracted the tumor immunotherapy in a mouse model.
conclusionsOur data support the hypothesis that many of the PPI adverse effects are caused by systematically compromised immunity, a result of PPI inhibition of the lysosomal enzymes. This novel mechanism complements the existing mechanisms in explaining the increased incidence of tumorigenesis and infectious diseases among PPI users and underlie the ongoing concern about the overuse of PPIs in adult and pediatric populations.
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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.