Preventive Effect of Water Containing Magnesium Ion on Paw Edema in Adjuvant-Induced Arthritis Rat

Nagai, Noriaki; Fukuhata, Takashi; Ito, Yoshimasa; Tai, Hideyuki; Hataguchi, Yoshihiro; Nakagawa, Koji

doi:10.1248/bpb.30.1934

Cited by 16 publications

(12 citation statements)

References 25 publications

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“…Recently, we reported that the oral administration of Mg 2+ to AA rats prevents the development of inflammation, 27) and that the co-administration of Mg 2+ and indomethacin suppresses hemorrhagic lesions in the gastric mucosa of AA rats. 24) In this study, we investigated the preventive effect of water containing Mg 2+ on loxoprofen-induced gastric lesions in AA rats.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…In addition, we previously reported that the co-administration of Mg 2+ does not affect the plasma IMC concentration. 17) These results show that MW can suppress the onset of the IMC-induced intestinal ulcers.…”

Section: 4)mentioning

confidence: 72%

“…Our previous reports showed that the oral administration of Mg 2+ to AA rats prevents the development of inflammation, and the combination of IMC and Mg 2+ provide an effective therapy of arthritic edema. 17) Therefore, these findings provide significant information that can be used to design further studies to develop potent NSAIDs that do not cause gastrointestinal toxicity.…”

Section: +mentioning

confidence: 94%

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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“…The joint diameter and functional parameters given below were scored before injecting FCA, daily for first 3 days and then every alternate day till day 16, a time when these scores normalized in arthritic control. A time-course for increase in joint diameter from day 0 values was plotted and the area under doi: 10.7243/2054-720X-1-1 curve (AUC) as an index of inflammation was determined [5]. The animals were sacrificed on day 16, joint tissue dissected out and stored at -80 o C for biochemical analysis.…”

Section: Following Groups (N=6) Were Includedmentioning

confidence: 99%

Calotropis procera latex proteins ameliorate functional limitations associated with adjuvant induced inflammation in rat

Kumar¹,

Chaudhary²,

Oliveira³

et al. 2014

Musculoskelet Biol

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Background: Proteins isolated from the latex (LP) of Calotropis procera (family: Apocynaceae) have been shown to ameliorate inflammatory hyperalgesia in the rat model of Freund's Complete Adjuvant (FCA) induced monoarthritis. The objective of the present study was to evaluate the effect of LP on inflammation index and time of functional recovery in arthritic rats. Methods: Monoarthritis was induced by intra-articular injection of FCA and joint diameter, motility, stair climbing ability and dorsal flexion pain scores were recorded before inducing arthritis and thereafter at different time intervals till joint functions recovered (day 16). The area under curve (AUC) for increase in joint diameter was calculated. The rats were sacrificed and the tissue levels of reduced glutathione and thiobarbituric acid reactive substances were measured. Histological analysis of the joint was also carried out. The effect of LP (5 and 25 mg/kg) and diclofenac (5 mg/kg) given on alternate days was evaluated on the parameters mentioned. Results: LP produced a dose-dependent reduction in AUC for increase in joint diameter and the time required to attain the normal joint functions as compared to the arthritic controls. Treatment with LP normalized the levels of oxidative stress markers and preserved tissue architecture. The protection afforded by LP was comparable to that with diclofenac.Conclusion: The present study shows that by inhibiting inflammation, LP fraction of latex of C. procera ameliorates functional limitations in arthritic rats.

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Preventive Effect of Water Containing Magnesium Ion on Paw Edema in Adjuvant-Induced Arthritis Rat

Abstract: ᭹, AA rats administered IM (2 mg/kg) and PW; ᭺, AA rats administered IM (2 mg/kg) and BW-5. The data are presented as meansϮS.E. of 5 independent rats.

Cited by 16 publications

References 25 publications

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

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

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

Calotropis procera latex proteins ameliorate functional limitations associated with adjuvant induced inflammation in rat

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