Small Bowel Tissue Concentration of Rebamipide: Study of Two Dosages in Healthy Subjects

Akamatsu, Taiji; Nagaya, Tadanobu; Ichikawa, Shinya; Sudo, T; Takeda, Ryutaro; Takenaka, Kazuhiro; Kodama, Ryo; Ito, Tetsuya; Arakura, Norikazu; Tanaka, Eiji

doi:10.3164/jcbn.10-86

Cited by 8 publications

(5 citation statements)

References 22 publications

(17 reference statements)

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“…HPLC was employed for the study of the concentration change of rebamipide in the small bowel tissue of healthy subjects. It was established that the concentration of rebapimide in the jejunum is sufficient to protect for NSAID-induced gastrointestinal complications [8]. SPE followed by ultra high performance liquid chromatography (UHPLC) was employed for the simultaneous analysis of blockers (Sotalol SOT, metoprolol MET, propanolol PRO), NSAIDs (paracetamol PAR, ketoprofen KET, salicilic acid SAL), and their metabolites (paracetamol sulfate PAR-S, paracetamol glucuronide PAR-G, ketoprofen glucuronide KET-G, o-desmethylmetoprolol D-MET, -hydroxymetoprolol MET-H, 4 ' -hydroxypropanolol sulfate PRO-S).…”

Section: Human Studiesmentioning

confidence: 99%

Cancer and the Cellular Response to Hypoxia

Adamaki¹,

Georgountzou²,

Moschovi³

2013

Pediat Therapeut

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The newest results in the chromatographic analysis of non-steroidal anti-inflammatory drugs present in various organic and inorganic accompanying matrices are collected and critically evaluated. Examples for the application of pre-concentration and pre-purification methods for the enhancement of the selectivity and sensitivity of chromatographic technologies are presented. The advantages and disadvantages of the different chromatographic methods are discussed and the separation capacities of the techniques are compared. The application of various chromatographic procedures for the separation and quantitative determination of non-steroidal anti-inflammatory drug (ibuprofen, diclofenac, genfibrozil, ketoprofen, diflunisal, indoprofen, fenoprofen, meclofenamic acid, naproxen, mexiletin) is discussed in detail.

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Section: Human Studiesmentioning

confidence: 99%

Cancer and the Cellular Response to Hypoxia

Adamaki¹,

Georgountzou²,

Moschovi³

2013

Pediat Therapeut

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“…In addition to stomach, recent clinical examinations revealed the injuries of small intestinal mucosa by the administration of NSAIDs more commonly than previously expected. ( 4 , 11 ) Although the pathogenesis of NSAID-induced small intestinal injuries is much less well understood than that of gastric injuries, it has recently been proposed that impairment of oxidative phosphorylation in mitochondria and subsequent O 2 •− production as the main underlying mechanism. ( 4 , 12 – 14 ) We thus hypothesized that mitochondrial O 2 •− production and lipid peroxidation may also be involved in BP-induced small intestinal mucosal injury.…”

Section: Introductionmentioning

confidence: 99%

Bisphosphonate-induced gastrointestinal mucosal injury is mediated by mitochondrial superoxide production and lipid peroxidation

Nagano

Matsui

Shimokawa

et al. 2012

J. Clin. Biochem. Nutr.

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Bisphosphonates such as alendronate and risedronate are commonly used for the treatment of postmenopausal osteoporosis. They have the gastrointestinal adverse effects such as erosions and ulcers in stomach and small intestine. However, the detailed biological mechanism remains to be elucidated. Since alendronate is suggested to increase the risk of non-steroidal anti-inflammatory drug-related gastropathy, we hypothesized that bisphosphonates and non-steroidal anti-inflammatory drugs have the same pathophysiological mechanisms in gastrointestinal mucosa: Bisphosphonates may induce cellular lipid peroxidation by inducing the production of mitochondrial superoxide. We also hypothesized that geranylgeranylacetone, an antiulcer drug, may prevent lipid peroxidation by reducing superoxide production. We treated gastric RGM1 cells and small intestinal IEC6 cells with alendronate or risedronate, and examined cellular injury, lipid peroxidation and superoxide production with specific fluorescent dyes, and underwent electron paramagnetic resonance spectroscopy to detect the production of superoxide in vitro. The results indicated that bisphosphonates indeed induced cellular injury, cellular lipid peroxidation, and superoxide production. We also demonstrated that the pretreatment of geranylgeranylacetone decreased superoxide production and prevented cellular lipid peroxidation. These results suggested that bisphosphonates, like non-steroidal anti-inflammatory drugs, induce lipid peroxidation by producing mitochondrial superoxide, which was prevented by geranylgeranylacetone.

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“…1), thereby suggesting increased production of intracellular mucin. The Reb concentration (10 µM) used in this study was thought to be a clinical relevant concentration, since the concentration of Reb in the human jejunum has been reported to be higher than 10 µM at 3 h after oral intake of Reb (100 mg) (20), which is the dosage used in clinical practice.…”

Section: Resultsmentioning

confidence: 99%

Rebamipide upregulates mucin secretion of intestinal goblet cells via Akt phosphorylation

Yasuda-Onozawa

Handa

Naito

et al. 2017

Molecular Medicine Reports

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Mucin is produced and secreted by epithelial goblet cells and is a key component of the innate immune system, acting as a barrier in the intestinal tract. However, no studies have been conducted investigating the increase in mucin secretion to enhance the intestinal barrier function. The present study investigated whether rebamipide (Reb) acts as a secretagogue of intestinal mucin and the underlying mechanisms involved, thereby focusing on the effect on goblet cells. The LS174T cell line was used as goblet cell‑like cells. Using Reb‑treated LS174T cells, the level of mucin content was assessed by periodic acid‑Schiff (PAS) staining, and mucin 2, oligomeric mucus/gel‑forming (MUC2) mRNA expression was assessed using quantitative polymerase chain reaction (PCR). Furthermore, MUC2 secretion in the supernatant was quantified by the dot blot method. The present study additionally investigated the involvement of the epidermal growth factor receptor/Akt serine/threonine kinase 1 (Akt) pathway in mucin secretion by western blotting. The results suggested that Reb strongly enhanced the positivity of PAS staining in LS174T cells, thereby suggesting increased intracellular mucin production. The PCR results indicated that Reb significantly increased MUC2 mRNA in whole cell lysate of LS174T cells. In order to assess the subsequent secretion of mucin by LS174T, MUC2 protein expression in the supernatant was assessed using the dot blot method and it was demonstrated that Reb significantly increased the secretion of MUC2 in a concentration‑dependent manner. The p‑Akt was significantly increased by Reb treatment, and an Akt inhibitor specifically suppressed MUC2 secretion. Overall, Reb increased mucin secretion directly via p‑Akt. Reb‑increased mucin may act as a strong non‑specific barrier against pathogenic stimulants in various intestinal diseases.

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Small Bowel Tissue Concentration of Rebamipide: Study of Two Dosages in Healthy Subjects

Cited by 8 publications

References 22 publications

Cancer and the Cellular Response to Hypoxia

Cancer and the Cellular Response to Hypoxia

Bisphosphonate-induced gastrointestinal mucosal injury is mediated by mitochondrial superoxide production and lipid peroxidation

Rebamipide upregulates mucin secretion of intestinal goblet cells via Akt phosphorylation

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