Rebamipide suppresses diclofenac-induced intestinal permeability<i>via</i>mitochondrial protection in mice

Diao, Lei; Qiao, Mu; Xu, Jianming; Liu, Xiao-Chang; Hu, Jing; Jin, Juan; Yao, Qiang; Chen, Moli

doi:10.3748/wjg.v18.i10.1059

Cited by 30 publications

(12 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…FITC-D and Evans blue are non-absorbed macromolecules that are used as indicators of intestinal permeability [22]. In our study, we found that treatment with ghrelin significantly attenuated FITC-D and Evans blue leakage following ICH, thus reducing the intestinal permeability.…”

Section: Discussionsupporting

confidence: 52%

Ghrelin Attenuates Intestinal Barrier Dysfunction Following Intracerebral Hemorrhage in Mice

Cheng

Wei

Yang

et al. 2016

IJMS

View full text Add to dashboard Cite

Intestinal barrier dysfunction remains a critical problem in patients with intracerebral hemorrhage (ICH) and is associated with poor prognosis. Ghrelin, a brain-gut peptide, has been shown to exert protection in animal models of gastrointestinal injury. However, the effect of ghrelin on intestinal barrier dysfunction post-ICH and its possible underlying mechanisms are still unknown. This study was designed to investigate whether ghrelin administration attenuates intestinal barrier dysfunction in experimental ICH using an intrastriatal autologous blood infusion mouse model. Our data showed that treatment with ghrelin markedly attenuated intestinal mucosal injury at both histomorphometric and ultrastructural levels post-ICH. Ghrelin reduced ICH-induced intestinal permeability according to fluorescein isothiocyanate conjugated-dextran (FITC-D) and Evans blue extravasation assays. Concomitantly, the intestinal tight junction-related protein markers, Zonula occludens-1 (ZO-1) and claudin-5 were upregulated by ghrelin post-ICH. Additionally, ghrelin reduced intestinal intercellular adhesion molecule-1 (ICAM-1) expression at the mRNA and protein levels following ICH. Furthermore, ghrelin suppressed the translocation of intestinal endotoxin post-ICH. These changes were accompanied by improved survival rates and an attenuation of body weight loss post-ICH. In conclusion, our results suggest that ghrelin reduced intestinal barrier dysfunction, thereby reducing mortality and weight loss, indicating that ghrelin is a potential therapeutic agent in ICH-induced intestinal barrier dysfunction therapy.

show abstract

Section: Discussionsupporting

confidence: 52%

Ghrelin Attenuates Intestinal Barrier Dysfunction Following Intracerebral Hemorrhage in Mice

Cheng

Wei

Yang

et al. 2016

IJMS

View full text Add to dashboard Cite

show abstract

“…Rat liver mitochondria were used for these studies, because purified healthy mitochondria from intestinal tissues could not be obtained in sufficient yields. However, it is accepted that there are no significant differences between mitochondria isolated from different organs in their response to uncoupling agents or inhibitors of the respiratory chain (Tyler, 1991;Diao et al, 2012). The liver mitochondrial suspension was then divided into two aliquots: one (2 mg/ml mitochondrial proteins) was used to evaluate the mitochondrial membrane potential, and the other one (0.8 mg/ml mitochondrial proteins) was used to characterize mitochondrial respiration by recording oxygen consumption.…”

Section: Methodsmentioning

confidence: 99%

NSAID-Induced Enteropathy: Are the Currently Available Selective COX-2 Inhibitors All the Same?

Fornai

Antonioli

Colucci

et al. 2013

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Nonsteroidal anti-inflammatory drugs (NSAIDs) can induce intestinal mucosal damage, but the underlying mechanisms remain poorly understood. The present study investigated the effects of celecoxib, etoricoxib, indomethacin, and diclofenac on small bowel integrity in rats. Male rats were treated orally with test drugs for 14 days. Animals were processed for assessment of blood hemoglobin levels and hepatic mitochondrial functions, microscopic evaluation of small intestinal damage, Western blot analysis of cyclooxygenase-1 and -2 (COX-1, COX-2) expression, and assay of malondialdehyde (MDA), myeloperoxidase (MPO), and prostaglandin E 2 (PGE 2 ) levels in small intestine. Indomethacin and diclofenac decreased blood hemoglobin levels, whereas etoricoxib and celecoxib were without effects. Celecoxib caused a lower degree of intestinal damage in comparison with the other test drugs. Indomethacin and diclofenac, but not etoricoxib or celecoxib, reduced intestinal PGE 2 levels. Test drugs did not modify intestinal COX-1 expression, although they enhanced COX-2, with the exception of celecoxib, which downregulated COX-2. Indomethacin, diclofenac, and etoricoxib altered mitochondrial respiratory parameters, although celecoxib was without effects. Indomethacin or diclofenac increased MDA and MPO levels in both jejunum and ileum. In the jejunum, etoricoxib or celecoxib did not modify such parameters, whereas in the ileum, etoricoxib, but not celecoxib, increased both MDA and MPO levels. These findings suggest that nonselective NSAIDs and etoricoxib can induce enteropathy through a topic action, whereas celecoxib lacks relevant detrimental actions. The selectivity profile of COX-1/COX-2 inhibition by test drugs and the related effects on prostaglandin production do not appear to play a major role in the pathogenesis of enteropathy.

show abstract

“…Cinaciguat did not influence jejunal strips, either when contracted by PGF 2 α or by carbachol; two different contractile agents were used to exclude the possibility that the non‐effect of cinaciguat is related to the contractile agent used, as it was reported before that different contractile agents can affect the ability to induce smooth muscle relaxation . Cinaciguat is expected to be more efficient when sGC is in the heme‐oxidized condition, but MDA/HNE levels in antrum and jejunum were similar to those in colon and fundus; the MDA/HNE values were also comparable to those reported in the literature for mouse small intestine (0.97 nmol/(mg protein)), rat small intestine (2.09 nmol/(mg protein)), and rat colon (1.17 nmol/(mg protein)) . We have thus no explanation for the lack of effect of cinaciguat in WT and apo‐sGC antrum and jejunum, nor for its ineffectiveness in the pylorus of apo‐sGC mice.…”

Section: Discussionmentioning

confidence: 95%

Influence of cinaciguat on gastrointestinal motility in apo‐sGC mice

Cosyns

Huyghe

Thoonen

et al. 2014

Neurogastroenterology Motil

View full text Add to dashboard Cite

show abstract

Rebamipide suppresses diclofenac-induced intestinal permeabilityviamitochondrial protection in mice

Abstract: Increased intestinal permeability induced by diclofenac can be attenuated by rebamipide, which partially contributed to the protection of mitochondrial function.

Cited by 30 publications

References 34 publications

Ghrelin Attenuates Intestinal Barrier Dysfunction Following Intracerebral Hemorrhage in Mice

Ghrelin Attenuates Intestinal Barrier Dysfunction Following Intracerebral Hemorrhage in Mice

NSAID-Induced Enteropathy: Are the Currently Available Selective COX-2 Inhibitors All the Same?

Influence of cinaciguat on gastrointestinal motility in apo‐sGC mice

Contact Info

Product

Resources

About