Experimental model in the qualitative and quantitative assessment of non-Helicobacter gastric microflora under proton pump inhibitors action

Filho, Augusto Diogo; Santos, Pablo Silva; Duque, Ânderson Silveira; Cezário, Renata Cristina; Filho, Paulo Pinto Gontijo

doi:10.1590/s0102-86502006000500003

Cited by 3 publications

(1 citation statement)

References 17 publications

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“…In this in vivo study we aimed to show how PPI leads to bone turnover and to provide an explanation of the exact mechanism. Based on clinical data suggesting that PPI increased fracture risk in a duration-or dose-dependent manner, we induced the long-term effects of PPI by administering 30 mg/kg for 8 weeks, which was longer than in previous rat model studies where rats ingested omeprazole 20-30 mg/kg for 4 days to 3 weeks (28)(29)(30).…”

Section: Discussionmentioning

confidence: 99%

The effect of a proton pump inhibitor on bone metabolism in ovariectomized rats

Joo

Park

Lee

et al. 2013

Molecular Medicine Reports

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Recent studies revealed that long-term intake of proton pump inhibitor (PPI) increases the risk of vertebral or hip fracture; however, the exact mechanism for this is not known. To evaluate the effect of long-term PPI therapy on bone turnover, we analyzed the signaling pathway involved in osteoclast differentiation and bone resorption/formation markers using ovariectomized rats. Six-week-old Sprague-Dawley (S-D) rats were ovariectomized, and two weeks later they were divided into four groups (group A, normal diet + placebo; group B, low calcium diet + placebo; group C, normal diet + PPI; and group D, low calcium diet + PPI). Omeprazole, at a concentration of 30 mg/kg, was administered orally for eight weeks and the rats were sacrificed when they were 16 weeks old. The relative expression levels of the receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) ratio, c-Fos, nuclear factor of activated T cells c1 (NFATc1) and osteocalcin in femoral bone marrow cells were compared, and serum C-terminal cross-linking telopeptide of type I (CTX-1) levels were determined. The relative ratio of RANKL/OPG was increased in group D, and gene expression levels of c-Fos and NFATc1 were upregulated in groups B and D, which are involved in differentiation and activation of osteoclasts. Furthermore, expression levels of osteocalcin, a bone formation marker, were decreased and levels of serum CTX-1, a bone resorption marker, were increased in group D. Taken together, a low calcium diet and PPI administration are thought to collaborate in order to alter osteoclast activity and bone resorption signaling.

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Section: Discussionmentioning

confidence: 99%

The effect of a proton pump inhibitor on bone metabolism in ovariectomized rats

Joo

Park

Lee

et al. 2013

Molecular Medicine Reports

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Membrane Transporters: Structure, Function and Targets for Drug Design

Ravna

Sager

Dahl

et al. 2008

Topics in Medicinal Chemistry

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Análise qualitativa das alterações anatomopatológicas na mucosa gástrica decorrentes da terapêutica prolongada com inibidores da bomba de prótons: estudos experimentais x estudos clínicos

Souza

Silva

Araújo

et al. 2013

ABCD, arq. bras. cir. dig.

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-Introduction: For a few decades the long-term use of proton pump inhibitors has had wide application in the treatment of several gastrointestinal diseases. Since then, however, several studies have called attention to the possible development of anatomical and pathological changes of gastric mucosa, resulting from the long term use of this therapeutic modality. Recent experimental and clinical studies suggest that these changes have connection not only to the development of precancerous lesions, but also of gastric tumors. Objective: To present a qualitative analysis of anatomical and pathological changes of gastric mucosa resulting from the long-term use of proton pump inhibitors. Method: The headings used were: proton pump inhibitors, precancerous lesions and gastric neoplasms for a non systematic review of the literature, based on Medline, Lillacs and Scielo. Twelve articles were selected from clinical (9) and experimental (3) studies, for qualitative analysis of the results. Results: The gastric acid suppression by high doses of proton pump inhibitors induces hypergastrinemia and the consequent emergence of neuroendocrine tumors in animal models. Morphological changes most often found in these experimental studies were: enterochromaffin-like cell hyperplasia, neuroendocrine tumor, atrophy, metaplasia and adenocarcinoma. In the studies in humans, however, despite enterochromaffin-like cell hyperplasia, the other effects, neuroendocrine tumor and gastric atrophy, gastric metaplasia and or adenocarcinoma, were not identified. Conclusion: Although it is not possible to say that the long-term treatment with proton pump inhibitors induces the appearance or accelerates the development of gastric cancer in humans, several authors have suggested that prolonged administration of this drug could provoke the development of gastric cancer. Thus, the evidence demonstrated in the animal model as well as the large number of patients who do or will do a long-term treatment with proton pump inhibitors, justifies the maintenance of this important line of research. RESUMO -Introdução:Há algumas décadas o uso prolongado de inibidores de bomba de prótons tem tido ampla aplicação no tratamento de doenças gastrointestinais. Desde então, entretanto, vários estudos têm alertado para o possível desenvolvimento de alterações anatomopatológicas da mucosa gástrica, decorrentes do uso prolongado desta modalidade terapêutica. Estudos clínicos e experimentais recentes sugerem que estas alterações teriam relação com o desenvolvimento não só de lesões pré-neoplásicas mas, também, de tumores gástricos. Objetivo: Apresentar uma análise qualitativa das alterações antomopatológicas da mucosa gástrica decorrentes do uso prolongado dos inibidores da bomba de prótons. Métodos -Foram utilizados os descritores inibidores da bomba de prótons, lesões pré-neoplásicas e neoplasias gástricas para revisão não sistemática narrativa da literatura, com base nas plataformas Medline, Lillacs e Scielo. Foram selecionados 12 artigos, dentre estudos clíni...

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Experimental model in the qualitative and quantitative assessment of non-Helicobacter gastric microflora under proton pump inhibitors action

Cited by 3 publications

References 17 publications

The effect of a proton pump inhibitor on bone metabolism in ovariectomized rats

The effect of a proton pump inhibitor on bone metabolism in ovariectomized rats

Membrane Transporters: Structure, Function and Targets for Drug Design

Análise qualitativa das alterações anatomopatológicas na mucosa gástrica decorrentes da terapêutica prolongada com inibidores da bomba de prótons: estudos experimentais x estudos clínicos

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