Preventive Effect of Co-administration of Water Containing Magnesium Ion on Indomethacin Induced Lesions of Gastric Mucosa in Adjuvant-Induced Arthritis Rat

• Published in: Biological & Pharmaceutical Bulletin Vol. 32; no. 1; pp. 116 - 120
• Main Authors: Nagai, Noriaki, Fukuhata, Takashi, Ito, Yoshimasa, Usui, Shigeyuki, Hirano, Kazuyuki
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.01.2009; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: adjuvant-induced arthritis; Animals; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Arthritis, Experimental - drug therapy; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Edema - chemically induced; Edema - drug therapy; gastric lesion; Gastric Mucosa - drug effects; Gastric Mucosa - pathology; Gene Expression Regulation - drug effects; indomethacin; Indomethacin - adverse effects; Magnesium - therapeutic use; magnesium ion; Male; Mineral Waters - therapeutic use; Mycobacterium; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; Rats; rheumatoid arthritis; RNA, Messenger - metabolism; Stomach Diseases - chemically induced; Stomach Diseases - prevention & control; Time Factors
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.32.116

It is well known that nonsteroidal anti-inflammatory drugs (NSAIDs) have significant side effects, such as gastroenteropathy, and that rheumatoid arthritis patients taking NSAIDs are more susceptible to NSAIDs-induced gastric lesions as compared with patients with other diseases. We demonstrate the preventive effect of the co-administration of bittern water (BW, nigari-sui in Japanese), which enables the effective intake of Mg2+, on the ulcerogenic response to indomethacin in adjuvant-induced arthritis (AA) rats. Four kinds of BW with different Mg2+ contents; ranging from 10—200 mg/l Mg2+ (BW-10, 25, 50, 200) were used in this study. Arthritis was induced by the injection of 50 μl of a suspension of 10 mg/ml heat-killed butyricum (Mycobacterium butyricum) in Bayol F oil into the plantar region of the right hind foot and tail of rats. Oral administration of indomethacin (40 mg/kg) caused hemorrhagic lesions in the gastric mucosa of AA rats at 14 d after adjuvant injection, and the lesion score of AA rats administered indomethacin was significantly higher than that of normal rats administered indomethacin. The expression of the mRNA for inducible nitric oxide synthase (iNOS) mRNA expression and the production of nitric oxide (NO) in the gastric mucosa of AA rats were also increased by the administration of indomethacin. The co-administration of BWs decreased the ulcerogenic response to indomethacin in AA rats. In addition, the administration of BW attenuated the increase in iNOS mRNA expression and NO production in AA rats receiving indomethacin. The oral administration of Mg2+ to AA rats had a potent preventive effect on the ulcerogenic response to indomethacin in AA rats, probably due to an inhibition in the rise in iNOS and NO levels in the gastric mucosa.