Protective effect of lafutidine, a histamine H<sub>2</sub> receptor antagonist, against loxoprofen‐induced small intestinal lesions in rats

Amagase, Kikuko; Ochi, Akimu; Sugihara, Tetsuya; Kato, Shinichi; Takeuchi, Koji

doi:10.1111/j.1440-1746.2010.06223.x

Cited by 24 publications

(19 citation statements)

References 33 publications

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“…As shown in Fig. 1B, the expression of iNOS mRNA was upregulated in the intestinal mucosa 6 h after the loxoprofen treatment, consistent with previous results obtained with other NSAIDs (10,11,22). The upregulation of iNOS expression was markedly suppressed by pretreatment with 1% MSG for 5 days, confirming a close relationship between enterobacterial invasion and iNOS expression (22).…”

Section: Mechanism Underlying Msg-induced Intestinal Protectionsupporting

confidence: 80%

“…Loxoprofen (10 -60 mg/kg), administered orally to fed rats, dose-dependently produced multiple hemorrhagic lesions in the small intestine 24 h later, mainly in the jejunum and ileum, similar to other conventional NSAIDs, and the severity of the lesions generated by loxoprofen at 60 mg/kg was almost equivalent to that caused by indomethacin at 10 mg/kg (10,11). Following the administration of loxoprofen at 60 mg/kg, the level of prostaglandin (PG) E 2 in the intestinal mucosa significantly decreased 2 h later, the effect persisting for about 24 h (9).…”

Section: Effect Of Dietary Msg On Loxoprofen-induced Intestinal Damagementioning

confidence: 93%

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New Therapeutic Strategy for Amino Acid Medicine: Prophylactic and Healing Promoting Effect of Monosodium Glutamate Against NSAID-Induced Enteropathy

et al. 2012

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Abstract.We reviewed the effect of monosodium glutamate (MSG) on the development and healing of nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal lesions in rats. Loxoprofen (60 mg/kg, p.o.) induced lesions in the small intestine within 24 h, accompanied by a decrease of Muc2 expression and an increase in enterobacterial invasion and inducible nitric oxide synthase (iNOS) expression. These lesions were prevented when MSG was given as a mixture of powdered food for 5 days before the loxoprofen treatment. This effect of MSG was accompanied by an increase in Muc2 expression / mucus secretion as well as the suppression of bacterial invasion and iNOS expression. These intestinal lesions healed spontaneously within 6 days, but the process was impaired by the repeated administration of low-dose loxoprofen (30 mg/kg) for 5 days after the ulceration, with the decrease of vascular endothelial derived growth factor (VEGF) expression and angiogenesis. The healing-impairing effect of loxoprofen was prevented by feeding 5% MSG for 5 days after the ulceration. These results suggest that MSG not only prevents loxoprofen-induced small intestinal damage but also promotes a healing of these lesions; the former is functionally associated with the increase in Muc2 expression / mucus secretion and the suppression of bacterial invasion and iNOS expression, while the latter is associated with the stimulation of VEGF expression/angiogenesis.

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Section: Mechanism Underlying Msg-induced Intestinal Protectionsupporting

confidence: 80%

Section: Effect Of Dietary Msg On Loxoprofen-induced Intestinal Damagementioning

confidence: 93%

New Therapeutic Strategy for Amino Acid Medicine: Prophylactic and Healing Promoting Effect of Monosodium Glutamate Against NSAID-Induced Enteropathy

et al. 2012

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“…The intestinal ulcerogenic response to loxoprofen was also markedly suppressed by prior administration of ampicillin, an antibiotics, similar to that induced by indomethacin [26]. These findings were supported by the fact that NSAID-induced small intestinal lesions do not occur in germ-free animals or fasting animals [5,27], suggesting a major pathogenic role for enterobacteria in these lesions.…”

Section: Commentarysupporting

confidence: 72%

Lafutidine Protects the NSAID-Induced Small Intestinal Lesions Mediated by Capsaicin-Sensitive Afferent Neurons

Amagase¹,

Takeuchi²

2014

Capsaicin - Sensitive Neural Afferentation and the Gastrointestinal Tract: From Bench to Bedside

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“…33,35) In addition, Kato et al reported that excessive NO production via iNOS is related to an increased ulcerogenic response to NSAIDs including loxoprofen and indomethacin. 11,40) We show that the expression of iNOS mRNA and NO production in the gastric mucosa of normal and AA rats are increased by the administration of loxoprofen, and that these increases are significantly higher than those that occur in normal rats administered loxoprofen. In addition, the lesions and NO levels in AA rats administered loxoprofen are prevented by the administration of aminoguanidine, a selective inhibitor of iNOS (Fig.…”

Section: Discussionmentioning

confidence: 89%

Co-administration of Water Containing Magnesium Ion Prevents Loxoprofen-Induced Lesions in Gastric Mucosa of Adjuvant-Induced Arthritis Rat

Nagai

Takeda

Itanami

et al. 2012

Biological & Pharmaceutical Bulletin

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Non-steroidal anti-inflammatory drugs (NSAIDs) comprise one of the most frequently used classes of medicines in the world; however, NSAIDs have significant side effects, such as gastroenteropathy, and rheumatoid arthritis patients taking NSAIDs are more susceptible to NSAID-induced gastric lesions as compared to patients with other diseases. In Asian countries, loxoprofen has been used clinically for many years as a standard NSAID. We demonstrate the preventive effect of the co-administration of water containing magnesium ion (magnesium water, 1-200 µg/kg) on the ulcerogenic response to loxoprofen in adjuvant-induced arthritis (AA) rats. Oral administration of loxoprofen (100 mg/kg) caused hemorrhagic lesions in the gastric mucosa of AA rats 14 d after adjuvant injection, and, following loxoprofen administration, the lesion score of AA rats was significantly higher than that of normal rats. The expression of inducible nitric oxide synthase (iNOS) mRNA and nitric oxide (NO) production in the gastric mucosa of AA rats were also increased by the administration of loxoprofen, and the increase in lesions and NO were prevented by the administration of aminoguanidine, an iNOS inhibitor. The co-administration of magnesium water decreased the ulcerogenic response to loxoprofen in AA rats. In addition, the co-administration of magnesium water attenuated the increase in iNOS mRNA expression and NO production in AA rats receiving loxoprofen. These results suggest that the oral co-administration of magnesium water to AA rats has a potent preventive effect on the ulcerogenic response to loxoprofen, probably by inhibiting the rise in iNOS and NO levels in the gastric mucosa.

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Protective effect of lafutidine, a histamine H₂ receptor antagonist, against loxoprofen‐induced small intestinal lesions in rats

Abstract: Lafutidine protects the small intestine against loxoprofen-induced lesions, essentially mediated by the CSN, and this effect may be functionally associated with increased Muc2 expression/mucus secretion, an important factor in the suppression of bacterial invasion.

Cited by 24 publications

References 33 publications

New Therapeutic Strategy for Amino Acid Medicine: Prophylactic and Healing Promoting Effect of Monosodium Glutamate Against NSAID-Induced Enteropathy

New Therapeutic Strategy for Amino Acid Medicine: Prophylactic and Healing Promoting Effect of Monosodium Glutamate Against NSAID-Induced Enteropathy

Lafutidine Protects the NSAID-Induced Small Intestinal Lesions Mediated by Capsaicin-Sensitive Afferent Neurons

Co-administration of Water Containing Magnesium Ion Prevents Loxoprofen-Induced Lesions in Gastric Mucosa of Adjuvant-Induced Arthritis Rat

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Protective effect of lafutidine, a histamine H2 receptor antagonist, against loxoprofen‐induced small intestinal lesions in rats

Abstract: Lafutidine protects the small intestine against loxoprofen-induced lesions, essentially mediated by the CSN, and this effect may be functionally associated with increased Muc2 expression/mucus secretion, an important factor in the suppression of bacterial invasion.

Cited by 24 publications

References 33 publications

New Therapeutic Strategy for Amino Acid Medicine: Prophylactic and Healing Promoting Effect of Monosodium Glutamate Against NSAID-Induced Enteropathy

New Therapeutic Strategy for Amino Acid Medicine: Prophylactic and Healing Promoting Effect of Monosodium Glutamate Against NSAID-Induced Enteropathy

Lafutidine Protects the NSAID-Induced Small Intestinal Lesions Mediated by Capsaicin-Sensitive Afferent Neurons

Co-administration of Water Containing Magnesium Ion Prevents Loxoprofen-Induced Lesions in Gastric Mucosa of Adjuvant-Induced Arthritis Rat

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Protective effect of lafutidine, a histamine H₂ receptor antagonist, against loxoprofen‐induced small intestinal lesions in rats