Excessive Interleukin 18 Relate the Aggravation of Indomethacin-Induced Intestinal Ulcerogenic Lesions in Adjuvant-Induced Arthritis Rat

Nagai, Noriaki; Tanino, Tadatoshi; Ito, Yoshimasa

doi:10.1248/bpb.b15-00375

Cited by 7 publications

(9 citation statements)

References 35 publications

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“…CFA is composed of attenuated pathogenic bacteria, such as Enterobacter (Mycobacterium butyricum). Furthermore, pathogenic bacteria will release endotoxin compounds such as Lipopolysaccharide (LPS) [16]. CFA can cause dysbiosis, which is an imbalance between nonpathogenic and pathogenic bacteria, resulting in the dominance of pathogenic bacteria.…”

Section: Discussionmentioning

confidence: 99%

Repairing Cell Structure of Jejunum Tissue in RA-CFA Rat Model Improved by Caprine CSN1S2 Protein

Zaidah

Soewondo

Fatchiyah

2020

JELS

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We aimed to analyze the effect of CSN1S2 protein in Etawah crossbred goat milk and yogurt on the histopathology of the jejunum and the amount of cell damage in Complete Freund's adjuvant (CFA)-induced rheumatoid arthritis (RA) rats. The rats were divided into six groups: the untreated control rats (C), control rats were given CSN1S2 protein from Etawah crossbred goat milk (CM) or yogurt (CY), RA rats, RA rats given CSN1S2 protein from Etawah crossbred goat milk (RAM) or yogurt (RAY). Hematoxylin-eosin staining was conducted for the histopathological analysis of jejunum. Statistical analysis was done using one-way ANOVA (a significance value of p ≤ 0.05) followed by the Tukey test. Our study observed that the control, CM, and CY group have a normal histological structure of jejunum. The damage to the jejunum structure was reported in the RA group. The milk CSN1S2 protein was able to improve the structure of jejunum villi and increase the normal cell number in the jejunum of the RA group, similar to control. The RAY group showed an impaired jejunum structure and a high number of necrotic cells as in the RA group.

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Section: Discussionmentioning

confidence: 99%

Repairing Cell Structure of Jejunum Tissue in RA-CFA Rat Model Improved by Caprine CSN1S2 Protein

Zaidah

Soewondo

Fatchiyah

2020

JELS

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“…In order to study the therapeutic effects of RBM on NSAID-induced GI injuries in RA patients, it is important to choose an appropriate animal model. RA is a chronic autoimmune disease associated with increases in tumor necrosis factor α, IL-6, IL-17, IL-18, rheumatoid factor, and other pro-inflammatory cytokines [5,6,33,34,35]. The onset of RA causes tenderness, joint swelling, synovial hyperplasia, and chronic inflammation, and the one therapeutic approach for RA used to alleviate pain is through NSAIDs.…”

Section: Discussionmentioning

confidence: 99%

“…These multiple factors lead to the mucosal injuries in the small intestine. In addition, it is known that patients with rheumatoid arthritis (RA) are more sensitive in their NO production system via iNOS and interleukin (IL)-18 [5,6], and are reportedly more susceptible to NSAID-induced GI injuries when compared with other NSAID users [7,8].…”

Section: Introductionmentioning

confidence: 99%

Solid Nanocrystals of Rebamipide Promote Recovery from Indomethacin-Induced Gastrointestinal Bleeding

Nagai

Sakamoto

Yamamoto

et al. 2019

IJMS

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Indomethacin (IMC)-induced gastrointestinal (GI) injuries are more common in rheumatoid arthritis (RA) patients than in other IMC users, and the overexpression of nitric oxide (NO) via inducible NO synthase (iNOS) is related to the seriousness of IMC-induced GI injuries. However, sufficient strategies to prevent IMC-induced GI injuries have not yet been established. In this study, we designed dispersions of rebamipide (RBM) solid nanocrystals (particle size: 30–190 nm) by a bead mill method (RBM-NDs), and investigated whether the oral administration of RBM-NDs is useful to prevent IMC-induced GI injuries. The RBM nanocrystals were spherical and had a solubility 4.71-fold greater than dispersions of traditional RBM powder (RBM-TDs). In addition, the RBM-NDs were stable for 1 month after preparation. The RBM contents in the stomach, jejunum, and ileum of rats orally administered RBM-NDs were significantly higher than in rats administered RBM-TDs. Moreover, the oral administration of RBM-NDs decreased the NO levels via iNOS and area of the GI lesions in IMC-stimulated RA (adjuvant-induced arthritis rat) rats in comparison with the oral administration of RBM-TDs. Thus, we show that the oral administration of RBM-NDs provides a high drug supply to the GI mucosa, resulting in a therapeutic effect on IMC-induced GI injuries. Solid nanocrystalline RBM preparations may offer effective therapy for RA patients.

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“…We previously reported that the excessive expression of interleukin (IL)-18 is related to the induction of iNOS, NO and interferon-γ in the intestinal mucosa of AA rats administered IMC. 21) Therefore, we are now planning to investigate the relationship between Mg 2+ and IL-18 expression in the small intestinal mucosa of IMC-administered AA rats.…”

Section: +mentioning

confidence: 99%

Co-administration of Magnesium Ion Prevents Indomethacin-Induced Intestinal Ulcerogenic Lesions in Adjuvant-Induced Arthritis Rats

Nagai

Ueno

Tanino

et al. 2017

Biological & Pharmaceutical Bulletin

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In a study to find ways to prevent the side effects of indomethacin (IMC), we previously reported that magnesium ion (Mg 2 ) can prevent the onset of IMC-induced gastric mucosa in adjuvant-induced arthritis (AA) rats, a model for rheumatoid arthritis (RA). In this study we investigated whether the co-administration of IMC and Mg 2 prevents the formation and aggravation of intestinal ulcerogenic lesions in AA rats. The single oral administration of an excessive dose of IMC (40 mg/kg) induces hemorrhagic lesions and nitric oxide (NO) production via inducible nitric oxide synthase (iNOS) in the jejunal and ileal mucosa of AA rats, and the extent of the lesions, as well as iNOS and NO levels in AA rats are higher than in normal rats. On the other hand, the co-administration of 200 mg/kg Mg 2 attenuates intestinal ulceration and the elevation in the iNOS and NO levels in AA rats. Further, hemorrhagic lesioning and enhanced iNOS and NO levels in AA rats also result from the repetitive oral administration of 3 mg/kg IMC (therapeutic dose) for 42 d (once a day), and these changes are also prevented by the co-administration of 200 mg/kg Mg 2 . In conclusion, the co-administration of Mg 2 suppresses the ulcerogenic response to IMC in the jejunal and ileal mucosa of AA rats, probably by preventing the elevation of iNOS and NO levels in the region. ; however, it is well known that the oral administration of these drugs leads to gastroenteropathy as a significant side effects, 2) and that RA patients taking NSAIDs are more susceptible to NSAIDs-induced intestinal ulcerogenic lesions than other patients or control subjects.2-4) Therefore, the development of NSAIDs that do not cause gastroenteropathy or other significant side effects is highly desired.It has been reported that a decrease in prostaglandins and excessive production of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) are related to the formation and pathogenesis of intestinal ulceration induced by NSAIDs. [4][5][6][7][8][9][10][11] In addition, we previously reported that the co-administration of magnesium ion (Mg 2+ ) and NSAIDs (indomethacin (IMC) and loxoprofen) prevents the increase in iNOS and NO production in the gastric mucosa, resulting in the inhibition of the onset of NSAIDs-induced gastric lesions.12,13) Therefore, the co-administration of Mg 2+ may also suppress the onset of intestinal ulcerogenic lesions by NSAIDs, and lead to develop a method for administering NSAIDs that will not lead to gastroenteropathy.The changes in the biological characteristics of adjuvantinduced arthritis (AA) rats correspond to those that occur in human RA. 2,4,14,15) Moreover, AA rats have been reported to show gastric and small intestinal mucosal lesions induced by IMC, naproxen, and aspirin. 2,4) In addition, the gastric and small intestinal mucosal lesions in AA rats administered conventional NSAIDs are significantly aggravated as compared with normal rats.2,4) These findings suggest the AA rats may provide a useful model for studies on the suppression ...

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Excessive Interleukin 18 Relate the Aggravation of Indomethacin-Induced Intestinal Ulcerogenic Lesions in Adjuvant-Induced Arthritis Rat

Cited by 7 publications

References 35 publications

Repairing Cell Structure of Jejunum Tissue in RA-CFA Rat Model Improved by Caprine CSN1S2 Protein

Repairing Cell Structure of Jejunum Tissue in RA-CFA Rat Model Improved by Caprine CSN1S2 Protein

Solid Nanocrystals of Rebamipide Promote Recovery from Indomethacin-Induced Gastrointestinal Bleeding

Co-administration of Magnesium Ion Prevents Indomethacin-Induced Intestinal Ulcerogenic Lesions in Adjuvant-Induced Arthritis Rats

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