• acute pancreatitis
• cerulein
• esomeprazole
• inflammation

• Animals
• Esomeprazole/pharmacology
• Esomeprazole/therapeutic use
• Rats, Wistar
• Rats
• Male
• Pancreatitis/drug therapy
• Pancreatitis/complications
• Pancreas/drug effects
• Pancreas/pathology
• Disease Models, Animal
• Lung Injury/drug therapy
• Tumor Necrosis Factor-alpha/blood
• Tumor Necrosis Factor-alpha/analysis
• Lung/drug effects
• Amylases/blood
• Acute Disease

• 2019/091 The study was funded with the support of the Kırıkkale University Scientific Research Project Board of with the project number 2019/091.

• Toll-like receptor
• chemotaxis
• cytokine profile
• infection
• innate immune response
• myeloid phagocyte system
• omeprazole

• Proton Pump Inhibitors/adverse effects
• Proton Pump Inhibitors/pharmacology
• Neutrophils/immunology
• Neutrophils/drug effects
• Neutrophils/metabolism
• Humans
• Macrophages/immunology
• Macrophages/drug effects
• Macrophages/metabolism
• Animals
• Phagocytosis/drug effects
• Reactive Oxygen Species/metabolism
• Signal Transduction/drug effects

• T32 AI141349 NIAID NIH HHS
• National Institute of Allergy and Infectious Diseases

• contact hypersensitivity
• dysbiosis
• gut microbiota
• immunomodulation
• omeprazole
• proton pump inhibitors

• Animals
• Proton Pump Inhibitors/adverse effects
• Proton Pump Inhibitors/pharmacology
• Gastrointestinal Microbiome/drug effects
• Gastrointestinal Microbiome/immunology
• Th17 Cells/immunology
• Th17 Cells/metabolism
• Mice
• T-Lymphocytes, Regulatory/immunology
• Dysbiosis
• Omeprazole/pharmacology
• Disease Models, Animal
• Cytokines/metabolism
• Female
• Mice, Inbred C57BL
• Dermatitis, Contact/immunology
• Dermatitis, Contact/etiology

• famotidine
• immunomodulatory
• lymphocyte ratio (NLR)
• neutrophil
• omeprazole

• Animals
• Dogs
• Dog Diseases/drug therapy
• Retrospective Studies
• Famotidine/therapeutic use
• Famotidine/pharmacology
• Histamine H2 Antagonists/pharmacology
• Histamine H2 Antagonists/therapeutic use
• Female
• Male
• Omeprazole/therapeutic use
• Omeprazole/pharmacology
• Proton Pump Inhibitors/therapeutic use
• Proton Pump Inhibitors/pharmacology
• Leukocyte Count/veterinary
• Mastocytoma/veterinary
• Mastocytoma/drug therapy

• Crohn’s disease
• Drug safety
• Inflammatory bowel disease
• Proton pump inhibitor
• Ulcerative colitis

• Proton Pump Inhibitors/adverse effects
• Proton Pump Inhibitors/therapeutic use
• Humans
• Inflammatory Bowel Diseases/drug therapy
• Inflammatory Bowel Diseases/immunology
• Disease Progression
• Gastrointestinal Microbiome/drug effects
• Gastroesophageal Reflux/drug therapy

• antacid
• gastroesophageal reflux disease (gerd)
• idiopathic pulmonary fibrosis
• idiopathic pulmonary fibrosis and its comorbidities
• omeprazole
• pirfenidone
• proton-pump inhibitors (ppi)

• Eosinophilic oesophagitis < disease-based
• large intestine < organ-based
• oesophagus < organ-based
• small intestine < organ-based
• stomach and duodenum < organ-based

• Gastritis/diagnosis
• Gastritis/drug therapy
• Gastritis/epidemiology
• Retrospective Studies
• Eosinophilic Esophagitis/diagnosis
• Eosinophilic Esophagitis/drug therapy
• Eosinophilic Esophagitis/epidemiology
• Humans
• Eosinophilia
• Enteritis/diagnosis
• Enteritis/drug therapy
• Enteritis/epidemiology

• T32 DK007202 NIDDK NIH HHS
• 5T32DK007202-44 NIH HHS

• anti-inflammatory agents
• antioxidants
• antithrombin III
• apheresis
• metformin
• nitric oxide
• nuclear factor kappa B
• peptides
• polyphenols
• preeclampsia
• probiotics
• proton pump inhibitors
• short interfering RNA
• soluble fms-like tyrosine kinase 1
• statins
• vitamins

• Pregnancy
• Female
• Humans
• Pre-Eclampsia/prevention & control
• Pre-Eclampsia/diagnosis
• Cesarean Section
• Placentation
• Oxidative Stress
• Vascular Endothelial Growth Factor Receptor-1/metabolism

• aggregation-induced emission
• antibacterial effects
• good biocompatibility
• inflammatory site homing
• photothermal therapy

• Humans
• Photothermal Therapy
• Neutrophils
• Cytokines
• Nanoparticles
• Inflammation
• Anti-Bacterial Agents

• chemotherapy drugs
• drug–drug interactions
• efficacy
• immune checkpoint inhibitors
• proton pump inhibitors
• tyrosine kinase inhibitors

• Humans
• Proton Pump Inhibitors/adverse effects
• Neoplasms/drug therapy
• Treatment Failure
• Antineoplastic Agents
• Drug Interactions

• animal disease models
• respiratory system models

• Animals
• Mice
• Esomeprazole/pharmacology
• Transforming Growth Factor beta
• Prospective Studies
• Retrospective Studies
• Proton Pump Inhibitors/pharmacology
• Idiopathic Pulmonary Fibrosis/drug therapy
• Disease Models, Animal

• K23 HL150331 NHLBI NIH HHS
• R01 AR077445 NIAMS NIH HHS
• K01 HL118683 NHLBI NIH HHS
• T32 HL007747 NHLBI NIH HHS
• R56 AR077445 NIAMS NIH HHS
• R01 HL137703 NHLBI NIH HHS
• National Heart, Lung, and Blood Institute
• National Institutes of Health
• Cancer Prevention and Research Institutes of Texas
• Baylor College of Medicine

This review article outlines six molecular pathways that confer resistance of cancer cells to ionizing radiation, and describes how proton pump inhibitors (PPIs) may be used to overcome radioresistance induced by alteration of one or more of these signaling pathways. The inflammatory, adaptive, hypoxia, DNA damage repair, cell adhesion, and developmental pathways have all been linked to the resistance of cancer cells to ionizing radiation. Here we describe the molecular link between alteration of these pathways in cancer cells and development of resistance to ionizing radiation, and discuss emerging data on the use of PPIs to favorably modify one or more components of these pathways to sensitize cancer cells to ionizing radiation. Understanding the relationship between altered signaling pathways, radioresistance, and biological activity of PPIs may serve as a basis to repurpose PPIs to restore key biological processes that are involved in cancer progression and to sensitize cancer cells to radiation therapy.

Background: Proton-pump inhibitors (PPIs) block acid secretion from gastric parietal cells; however, recent studies have reported that PPIs have antioxidant and anti-inflammatory properties in various cells. Newer PPIs are stronger inhibitors of acid secretion; however, the anti-inflammatory effects of these drugs have not been assessed. We evaluated anti-inflammatory effect of PPIs on the development of asthma/asthma exacerbation (AE) in a national health screening cohort.

Methods: This case-control study comprised 64,809 participants with asthma who were 1:1 matched with controls from the Korean National Health Insurance Service-Health Screening Cohort. Conditional logistic regression analysis was used to evaluate the effect of previous PPI use on an asthma diagnosis in all participants. Unconditional logistic regression was used to assess the effect of PPI use on AE in participants with asthma. These relationships were estimated in a subgroup analysis according to PPI generation.

Results: Overall, PPI use increased the risk of asthma diagnosis [adjusted odds ratio (aOR) = 1.29, 95% confidence interval (CI) = 1.23–1.35, p < 0.001]. Use of the first-generation PPIs was associated with asthma (aOR = 1.34, 95% CI = 1.18–1.52, p < 0.001), while use of second-generation PPIs was not (aOR = 0.97, 95% CI = 0.82–1.15, p = 0.748). In contrast, overall PPI use decreased the risk of AE in participants with asthma (aOR = 0.79, 95% CI = 0.75–0.84, p < 0.001), although this effect was observed only for second-generation PPIs (aOR = 0.76, 95% CI = 0.65–0.89, p = 0.001).

Conclusion: PPI use increased the risk for subsequent asthma diagnosis. However, this effect was confined to first-generation PPIs. Second-generation PPIs decreased the risk of AE.

• National Research Foundation of Korea

Over the past decade, the role of proton pump inhibitor (PPI) medication has evolved from a diagnostic tool for Eosinophilic Esophagitis (EoE), by excluding patients with PPI responsive esophageal eosinophilia (PPI-REE), to a therapy for EoE. This transition resulted from the Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the Appraisal of Guidelines for Research and Evaluation II (AGREE) Conference to support PPI therapy for EoE in children and adults. Additional recent advances have suggested a role for genetic variations that might impact response to PPI therapy for EoE. This review article will explore a brief background of EoE, the evolution of PPI therapy for EoE and its proposed mechanisms, efficacy and safety in children and adults, and considerations for future PPI precision medicine in patients with EoE.

• Nemours Research Foundation

Current guideline conditionally recommends regular use of anti-reflux medication in idiopathic pulmonary fibrosis (IPF). However, the effect of anti-reflux therapy in this group remains controversial. We systematically reviewed literatures to evaluate whether anti-reflux therapy could ameliorate pulmonary function in IPF.

We performed electronic search in PubMed, Embase and CENTRAL (Cochrane Central Register of Controlled Trials) to identify original articles published in English language. We included randomized controlled trials (RCTs) and observational studies regarding anti-reflux therapy on pulmonary function in IPF. Qualitative and quantitative analyses were conducted. In quantitative analysis, the inverse-variance method with fixed-effect model was used to analyze pooled data.

Fifteen studies (2 RCTs and 13 observational studies) including 3,891 patients with IPF were included. Pooled analysis suggested that anti-reflux therapy did not improve forced vital capacity (FVC)% predicted [mean difference (MD) =0.88, 95% confidence interval (CI): −0.22 to 1.98, P=0.12, I² =0%, 8 studies, n=3,076], diffusing capacity of the lung for carbon monoxide (DLCO) % predicted (MD =0.75, 95% CI: −0.13 to 1.62, P=0.10, I² =0%, 8 studies, n=3,073), and FVC decline (MD =0.02, 95% CI: −0.01 to 0.04, P=0.29, I² =17%, 5 studies, n=1,586) in IPF.

Anti-reflux therapy may not ameliorate pulmonary function in IPF. However, adequately powered studies are warranted to validate the present findings.

• Anti-reflux therapy
• idiopathic pulmonary fibrosis
• pulmonary function

• Calcium
• Endothelial cells
• Endothelium-dependent relaxing factors
• Nitric oxide synthase
• Omeprazole

• Food allergy
• anaphylaxis
• mast cell
• omeprazole
• proton pump inhibitor

• Allergens/immunology
• Animals
• Cell Degranulation
• Cells, Cultured
• Cytokines/metabolism
• Disease Models, Animal
• Food Hypersensitivity/drug therapy
• Food Hypersensitivity/immunology
• Food Hypersensitivity/metabolism
• Food Hypersensitivity/pathology
• Humans
• Immunoglobulin E/immunology
• Inflammation Mediators/metabolism
• Mast Cells/drug effects
• Mast Cells/immunology
• Mast Cells/metabolism
• Mice
• Omeprazole/pharmacology
• Receptors, IgE/metabolism
• Signal Transduction/drug effects

• R01 AI142872 NIAID NIH HHS
• T32 GM107000 NIGMS NIH HHS
• T32 AI007512 NIAID NIH HHS
• P30 DK034854 NIDDK NIH HHS
• R01 DK097112 NIDDK NIH HHS
• R21 AI151591 NIAID NIH HHS
• R01 AI119918 NIAID NIH HHS

• Allergy
• Children
• Immunology
• Proton pump inhibitor
• Side effects

• Child
• Humans
• Proton Pump Inhibitors/adverse effects
• Proton Pump Inhibitors/pharmacology
• Proton Pump Inhibitors/therapeutic use

• Leukemias
• MLL fusion proteins
• MLL1 HMT activity
• MLL1-WDR5 interaction
• Proton pump inhibitors

Objective: A window period of approximately 3–6 months is usually adopted in studies that evaluate hepatic encephalopathy (HE) risk in proton pump inhibitor (PPI) users. However, HE risk after short-term PPI exposure remains unclear. We explored the effect of short-term PPI exposure using a case-crossover study design. Design: Records of patients with decompensated cirrhosis who had received an HE diagnosis were retrieved from the National Health Insurance Research Database. PPI use rates were compared for case and control with window periods of 7, 14, and 28 days. The adjusted self-matched odds ratio (OR) and 95% confidence interval (CI) from a conditional logistic regression model were used to determine the association between PPI use and HE risk. Results: Overall, 13 195 patients were analyzed. The adjusted OR for HE risk after PPI exposure was 3.13 (95% CI = 2.33–4.20) for the 7-day window, 4.77 (95% CI = 3.81–5.98) for the 14-day window, and 5.60 (95% CI = 4.63–6.78) for the 28-day window. All PPI categories, except omeprazole and pantoprazole, were associated with an increased HE risk. Irrespective of other precipitating factors, such as recent gastrointestinal bleeding or infection, PPI significantly increased HE risk. Conclusion: Short-term PPI use is significantly associated with HE in patients with decompensated cirrhosis. Physicians should use PPI in these patients for appropriate indications, and carefully monitor signs of HE even after short-term exposure. Owing to the limitations of retrospective design in the current study, further study is warranted to confirm our findings.

• Short-term Registry for Catastrophic Illness Patient Database
• hepatic encephalopathy
• proton pump inhibitor

There is a reported association between proton pump inhibitor (PPI) exposure and increased risk of Clostridium difficile infection (CDI), but less is known about how this class of medications taken during treatment might influence mortality after CDI. Here we examine 180-day mortality rates in a cohort of CDI elders and its association with exposure to PPIs. We conducted a retrospective cohort study of elderly patients (> 65 years of age) diagnosed and treated for CDI in the years 2014–2016 (n = 874) in the Umass Memorial Health Care system, which represents both academic and community healthcare. Patient characteristics and medication use was extracted from the electronic medical record (EMR) and 6 month mortality data was obtained via the Center for Disease Control National Death Index. A Cox proportional hazards model was used to estimate hazard ratios associated with medication exposures and other relevant variables.

Of the 874 elderly adults treated for CDI, 180-day all-cause mortality was 12.4%. Exposure to a PPI was associated with a 55% reduced risk of mortality (adjusted hazard ratio (aHR) 0.45; 95% confidence interval (CI) 0.28–0.72). In our Cox model, increasing age (aHR 1.45; 95% CI 1.14–1.84), those with severe CDI infections (aHR 1.87; 95% CI 1.22–2.88), and those with hospital acquired CDI (aHR 3.01; 95% CI 1.81–4.99) also had increased 180 day mortality risk. There were similar associations noted with both 90 day and 1-year mortality.

Use of PPIs during CDI treatment in elderly patients is associated with decreased 180-day mortality. Although use of PPIs has been associated with an increased risk of CDI, it appears to be protective against mortality when used during the treatment phase.

• Clostridium difficile
• Enteric pathogens
• Infectious disease
• Medication safety
• Proton pump inhibitors

Several studies have been conducted to explore the association between the use of proton pump inhibitors (PPIs) and hepatic encephalopathy (HE) risk in patients with liver cirrhosis. However, their results are controversial.

To perform a systematic review and meta-analysis to evaluate the HE risk among PPI users.

A systematic search on PubMed, Web of Science, EMBase, and ScienceDirect databases was conducted up to December 31, 2018 for eligible studies involving PPI use and HE risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the fixed or random effects model. Publication bias was evaluated using Begg’s test, Egger’s test, and trim-and-fill method.

Seven studies with 4574 patients were included in the present meta-analysis. The meta-analysis results indicated a significant association between the PPI use and HE risk (OR = 1.50; 95%CI: 1.25-1.75) with low heterogeneity (I² = 14.2%, P = 0.321). Although publication bias existed when Egger’s tests were used (P = 0.005), the trim-and-fill method verified the stability of the pooled result. Sensitivity analyses suggested that the results of this meta-analysis were robust.

The current evidence indicates that PPI use increases HE risk in patients with liver cirrhosis. Further studies with a large data set and well-designed models are needed to validate our findings.

• Proton pump inhibitors
• Hepatic encephalopathy
• Meta-analysis

• Hepatic Encephalopathy/epidemiology
• Hepatic Encephalopathy/etiology
• Humans
• Incidence
• Liver Cirrhosis/complications
• Proton Pump Inhibitors/adverse effects
• Risk Assessment
• Risk Factors

• PLGA-b-PEG nanoparticles
• curcumin analogue
• humoral immune response
• immunosuppression
• innate immune response
• αβ-unsaturated carbonyl-based compound

• Adaptive Immunity/drug effects
• Adaptive Immunity/immunology
• Animals
• Curcumin/analogs & derivatives
• Curcumin/chemical synthesis
• Curcumin/chemistry
• Curcumin/pharmacology
• Dose-Response Relationship, Drug
• Immunity, Innate/drug effects
• Immunity, Innate/immunology
• Immunosuppressive Agents/chemical synthesis
• Immunosuppressive Agents/chemistry
• Immunosuppressive Agents/pharmacology
• Male
• Mice
• Mice, Inbred BALB C
• Molecular Structure
• Nanoparticles/chemistry
• Piperidines/chemical synthesis
• Piperidines/chemistry
• Piperidines/pharmacology
• Polyethylene Glycols/chemistry
• Polyglactin 910/chemistry
• Sheep
• Structure-Activity Relationship

• association
• case-control study
• pharmacoepidemiology
• proton pump inhibitor
• tuberculosis

• Clostridium difficile
• Staphylococcus aureus
• bacteremia
• mortality
• proton-pump inhibitors

• BE progression
• CDX2
• Hedgehog signaling
• PPIs
• SOX9

• Community-acquired pneumonia
• antipsychotics
• inhaled corticosteroids
• proton pump inhibitors
• risk factors

• case-control study
• cholangiocarcinoma
• defined daily dose
• odds ratios
• proton pump inhibitors

The recent FDA approval of two drugs, pirfenidone and nintedanib, for the treatment of idiopathic pulmonary fibrosis (IPF) has fueled interest in the development of additional drugs to treat the disease or its major clinical complications including cough and acute exacerbations. Since 2015, there are at least a dozen active interventional studies that are testing the efficacy of novel pharmacotherapies, exercise or stem cells in modifying the disease process in IPF. Additionally, there are combinatorial studies evaluating the effectiveness of pirfenidone or nintedanib in combination with other agents. However, there remains an urgent need for clinical trials to prospectively evaluate the efficacy of existing drugs with promising retrospective data, such as proton pump inhibitors (PPIs), in IPF. Several retrospective cohorts have provided tantalizing data supporting the beneficial effect of PPIs in patients with well-defined IPF. This review provides the general outlook of pharmacotherapies in IPF, and highlights preclinical and retrospective clinical data to make a case for randomized controlled clinical trials of PPIs in IPF.

• IPF
• antacids
• clinical trials
• fibrosis
• generic drugs
• inflammation
• proton pump inhibitors

• CCl(4)
• Esomeprazole
• IL-6
• Liver fibrosis
• Proton pump inhibitors
• TGF-β

• Adult
• Cohort Studies
• Female
• Gastroesophageal Reflux/complications
• Humans
• Incidence
• Male
• Middle Aged
• Pneumonia/complications
• Taiwan

• Cardinal Tien Hospital
• National Health Research Institutes

• Gastrointestinal food allergy
• Network analyses
• Personalized medicine
• Precision medicine
• Randomized controlled trial
• Systems medicine

• Aged
• Clostridium Infections/epidemiology
• Diarrhea/chemically induced
• Drug Interactions
• Histamine H2 Antagonists/administration & dosage
• Histamine H2 Antagonists/adverse effects
• Humans
• Incidence
• Infections/epidemiology
• Infections/etiology
• Proton Pump Inhibitors/administration & dosage
• Proton Pump Inhibitors/adverse effects
• Risk

• antireflux surgery
• fibrosis
• gastroesophageal reflux
• lung inflammation
• proton pump inhibitors

• Case-control study
• Proton pump inhibitors
• Pyogenic liver abscess
• Taiwan

Patients with gastroesophageal reflux disease (GERD) present with comorbid complications with implications for healthcare utilization. To date, little is known about the effects of GERD treatment with a proton-pump inhibitor (PPI) on patients’ subsequent healthcare utilization for acute respiratory infections (ARIs). This population-based study compared ARI episodes captured through outpatient visits, one year before and one year after GERD patients received PPI treatment. We used retrospective data from the Longitudinal Health Insurance Database 2005 in Taiwan, comparing 21,486 patients diagnosed with GERD from 2010 to 2012 with 21,486 age-sex matched comparison patients without GERD. Annual ARI episodes represented by ambulatory care visits for ARI (visits during a 7-day period bundled into one episode), were compared between the patient groups during the 1-year period before and after the index date (date of GERD diagnosis for study patients, first ambulatory visit in the same year for their matched comparison counterpart). Multiple regression analysis using a difference-in-difference approach was performed to estimate the adjusted association between GERD treatment and the subsequent annual ARI rate. We found that the mean annual ARI episode rate among GERD patients reduced by 11.4%, from 4.39 before PPI treatment, to 3.89 following treatment (mean change = -0.5 visit, 95% confidence interval (CI) = (-0.64, -0.36)). In Poisson regression analysis, GERD treatment showed an independent association with the annual ARI rate, showing a negative estimate (with p<0.001). The study suggests that GERD treatment with PPIs may help reduce healthcare visits for ARIs, highlighting the importance of treatment-seeking by GERD patients and compliance with treatment.

Proton pump inhibitors (PPIs) are well-known antacid drugs developed to treat gastric disorders. Emerging studies demonstrate that PPIs possess biological activities that extend beyond inhibition of H⁺/K⁺ ATPase (proton pumps) expressed in parietal cells of the stomach. Some of the extra-gastric activities of PPIs include modulation of epithelial, endothelial, and immune cell functions. Recently, we reported that PPIs suppress the expression of several proinflammatory and profibrotic molecules, as well as enhance antioxidant mechanisms in order to favorably regulate lung inflammation and fibrosis in an animal model of bleomycin-induced lung injury. In addition, several retrospective clinical studies report that the use of PPIs is associated with beneficial outcomes in chronic lung diseases including idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Based on these preclinical and clinical observations, we hypothesized that PPIs ameliorate smoke-induced lung injury. Accordingly, we evaluated the pharmacological efficacy of the PPI esomeprazole in a mouse model of cotton smoke-induced lung injury. The animals were exposed to cotton smoke for 3-weeks in the presence or absence of esomeprazole treatment. We found that therapeutic administration of esomeprazole significantly inhibited the progression of fibrosis throughout the lungs of the animals in this group compared to controls. In addition, esomeprazole also reduced circulating markers of inflammation and fibrosis. Overall, our work extends the emerging anti-inflammatory and antifibrotic potential of PPIs and their role in modulation of chronic lung diseases.

• fibrosis
• inflammation
• lung injury
• proton pump inhibitors

• cyclic guanosine monophosphate
• guanosine monophosphate cyclique
• inhibiteurs de la pompe à proton
• neutrophiles polynucléaires
• nitric oxide
• nitric oxide synthase
• nitroblue tetrazolium test
• omeprazole
• oméprazole
• oxyde nitrique
• oxyde nitrique synthase
• p38 mitogen-activated protein kinase
• pantoprazole
• polymorphonuclear neutrophils
• proton pump inhibitors
• protéine kinase activée par l’agent mitogène p38
• test au nitrobleu de tétrazolium

• Acid Suppression
• Cognitive Dysfunction
• Gut Microbiota
• Liver Failure

• Gastrointestinal Diseases/drug therapy
• Humans
• Idiopathic Pulmonary Fibrosis/drug therapy
• Idiopathic Pulmonary Fibrosis/metabolism
• Idiopathic Pulmonary Fibrosis/physiopathology
• Practice Guidelines as Topic
• Proton Pump Inhibitors/chemistry
• Proton Pump Inhibitors/pharmacology
• Research Design

• K01 HL118683 NHLBI NIH HHS
• UM1 HL119089 NHLBI NIH HHS

The administration of supplemental oxygen to treat ventilatory insufficiency may lead to the formation of reactive oxygen species and subsequent tissue damage. Cytochrome P4501A1 (CYP1A1) can modulate hyperoxic lung injury by a currently unknown mechanism. Our objective was to evaluate the effect of administration of omeprazole on the induction of CYP1A1 and its influence on hyperoxic lung injury in an established preterm rabbit model.

Omeprazole was administered either (1) directly to the fetus, (2) to the mother or (3) after birth to the pups in different doses (2–10 or 20 mg/kg). Controls were injected with the same amount of saline. Pups were housed in normoxia (21 %) or hyperoxia (>95 %) for 5 days. Outcome parameters were induction of CYP1A1 measured by real-time polymerase chain reaction (RT-PCR) immediately after delivery, at day 3 and day 5 as well as lung function, morphometry and immunohistochemistry assessed at day 5 of life. Transcriptome analysis was used to define the targeted pathways.

Daily neonatal injections demonstrated a dose-dependent increase in CYP1A1. Lung function tests showed a significant improvement in tissue damping, tissue elasticity, total lung capacity, static compliance and elastance. Morphometry revealed a more developed lung architecture with thinned septae in animals treated with the highest dose (20 mg/kg) of omeprazole. Surfactant protein B, vascular endothelial growth factor and its receptor were significantly increased on immunohistochemical stainings after omeprazole treatment.

Neonatal administration of omeprazole induces CYP1A1 in a dose-dependent matter and combined pre- and postnatal administration attenuates hyperoxic lung injury in preterm rabbits, even with the lowest dose of omeprazole without clear CYP1A1 induction.

The online version of this article (doi:10.1186/s12967-016-1009-3) contains supplementary material, which is available to authorized users.

• Bronchopulmonary dysplasia
• CYP1A1
• Omeprazole
• Preterm
• Rabbit