Pantoprazole treatment does not invoke anti-inflammatory properties in vivo

Becker, T; Maróstica, Marta; Ribeiro, Marcelo Lima; Mendonça, Sérgio; Gambero, Alessandra; Pedrazzoli, José

doi:10.1016/j.intimp.2004.04.009

Cited by 10 publications

(8 citation statements)

References 19 publications

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“…In conclusion, the present study demonstrates that pantoprazole treatment in aged mice impairs fracture healing most probably by a too early stimulation of osteoclast activity, a downregulation of BMP-4 and antioxidant factors, as well as a disturbed ratio of angiogenic to osteogenic growth factors. www.nature.com/scientificreports/ same as was given in the previous study with young adult animals 18 and corresponds to doses used in various experimental studies [52][53][54] .…”

Section: Discussionmentioning

confidence: 99%

Pantoprazole impairs fracture healing in aged mice

Menger

Bremer

Scheuer

et al. 2020

Sci Rep

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Proton pump inhibitors (PPIs) belong to the most common medication in geriatric medicine. They are known to reduce osteoclast activity and to delay fracture healing in young adult mice. Because differentiation and proliferation in fracture healing as well as pharmacologic actions of drugs markedly differ in the elderly compared to the young, we herein studied the effect of the PPI pantoprazole on bone healing in aged mice using a murine fracture model. Bone healing was analyzed by biomechanical, histomorphometric, radiological and protein biochemical analyses. The biomechanical analysis revealed a significantly reduced bending stiffness in pantoprazole-treated animals when compared to controls. This was associated with a decreased amount of bone tissue within the callus, a reduced trabecular thickness and a higher amount of fibrous tissue. Furthermore, the number of osteoclasts in pantoprazole-treated animals was significantly increased at 2 weeks and decreased at 5 weeks after fracture, indicating an acceleration of bone turnover. Western blot analysis showed a lower expression of the bone morphogenetic protein-4 (BMP-4), whereas the expression of the pro-angiogenic parameters was higher when compared to controls. Thus, pantoprazole impairs fracture healing in aged mice by affecting angiogenic and osteogenic growth factor expression, osteoclast activity and bone formation.

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Section: Discussionmentioning

confidence: 99%

Pantoprazole impairs fracture healing in aged mice

Menger

Bremer

Scheuer

et al. 2020

Sci Rep

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“…So far, no other in vivo study has analyzed the effect of PPI on migration in human immune cells. The anti‐inflammatory effect of PPI was only investigated in a rat model but no significant inhibition of migration of PMN after stimulation with H. pylori was uncovered . However, these results are only transferable to a limited extent due to different experimental setups and examined species.…”

Section: Discussionmentioning

confidence: 99%

Proton-pump inhibitors elevate infection rate in cardiothoracic surgery patients by influencing PMN function in vitro and in vivo

Haas

Maywald

Goetzenich

et al. 2018

Journal of Leukocyte Biology

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Proton-pump inhibitors (PPI) as pantoprazole are highly effective acid suppressive agents that belong to the world's most sold medication. However, they are pronounced to have immunosuppressive aspects. In our study, a negative influence of PPI on functions of polymorphonuclear cells in vitro like phagocytosis, oxidative burst, chemotaxis, and killing activity was shown, whereas formation of neutrophil extracellular traps (NET)osis remained unaffected. Pantoprazole stimulation additionally reduced the production of the proinflammatory cytokine IL-1β in whole blood assay as well as the production of IL-2 and IFN-γ after whole blood stimulation with phytohaemagglutinin. Moreover, IFN-γ feedback mechanisms and signaling by STAT-1 was impaired by PPI. Cardiac surgery is accompanied by developing systemic inflammatory response syndrome with immunosuppressive aspects. We exhibited reduced oxidative burst analyzing cardiac surgery patients' samples receiving or not receiving PPI. Furthermore, a higher rate of infections in patients receiving permanent PPI medication in retrospective analysis was uncovered. Patients undergoing cardiac surgery with cardiopulmonary bypass and regular PPI medication developed significant more infections retrospectively indicating a clinical impact of the immunosuppressive influence of PPI.

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“…However, this inhibitory effect was not confirmed by another group [14]. Furthermore, at doses able to inhibit in vivo gastric acid secretion, omeprazole and pantoprazole, used either for short or long periods, failed to inhibit the neutrophil migration in response to carrageenan or Helicobacter pylori [15]. Thus, in order to further clarify whether PPI affects in vitro neutrophil chemotaxis, we investigated the ability of omeprazole and pantoprazole to inhibit the human neutrophil chemotaxis induced by both fMLP and interleukin-8 (IL-8).…”

Section: Introductionmentioning

confidence: 93%