FK506 is superior to methotrexate in therapeutic effects on advanced stage of rat adjuvant-induced arthritis

Sakuma, Shozo; Nishigaki, Fusako; Magari, Katsue; Ogawa, Toshikazu; Miyata, Susumu; Ohkubo, Y.; Goto, Toshio

doi:10.1007/pl00000227

Cited by 47 publications

(44 citation statements)

References 24 publications

(22 reference statements)

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“…It has been reported that patients with RA are more susceptible to NSAIDs-induced intestinal ulcerogenic lesions than other NSAIDs users. [3][4][5]17) Furthermore, it is well known that IMC has significant gastrointestinal toxicity as its main adverse effect. Therefore, we demonstrate the gastrointestinal toxicity in IMC-administered AA rats.…”

Section: Discussionmentioning

confidence: 99%

“…The adjuvant-induced arthritis (AA) rat is often used for the study of inflammatory pain during the development of AA is assessed by measuring paw volume (paw edema). 16,17) The paw edema in AA rats is observed the two inflammatory stages (primary and secondary inflammation). The primary inflammation starts from the day following the injection of adjuvant into the right hind foot, and the secondary inflammation is observed from 7 d after adjuvant injection.…”

mentioning

confidence: 99%

“…3,5) In addition, the changes in the biological characteristics of AA rats correspond to those that occur in human RA. 3,5,16,17) Therefore, AA rats may be an useful model for studies on the mechanisms of IMC-induced intestinal ulcerogenic lesions in RA.…”

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confidence: 99%

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

Nagai

Tanino

Ito

2015

Biological & Pharmaceutical Bulletin

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It is well known that rheumatoid arthritis patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) are more susceptible to NSAIDs-induced gastroenteropathy in comparison with other patients. In this study we demonstrate that expression levels of interleukin (IL)-18 are related to aggravation of intestinal ulcerogenic lesions in adjuvant-induced arthritis (AA) rats following oral administration of indomethacin. AA rats were administered oral indomethacin (40 mg/kg) and killed under deep isoflurane anesthesia after 24 h. The small intestinal mucosa was then examined. Oral administration of indomethacin caused hemorrhagic lesions in the small intestinal mucosa of AA rats, and the lesion score of AA rats 24 h after indomethacin treatment was approximately 5.6-fold higher than for normal rats administered indomethacin. IL-18 expression in the small intestinal mucosa of AA rats administered indomethacin was also higher in comparison with normal rats receiving indomethacin. In addition, interferon-γ and nitric oxide levels in the small intestinal mucosa of AA rats were increased following oral administration of indomethacin. It is possible that IL-18 expression in AA rats renders the small intestinal mucosa more sensitive to indomethacin, and that IL-18 may play a role in aggravating intestinal ulcerogenic lesions in AA rats treated with this drug.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

Nagai

Tanino

Ito

2015

Biological & Pharmaceutical Bulletin

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“…Inflammatory pain during the development of AA is assessed by measuring paw volume (paw edema). 38,39) Paw edema in AA rats is known to involve two inflammatory stages, primary and secondary inflammation. The primary inflammation starts from the day following the injection of adjuvant into the right hind foot.…”

Section: Gastric and Small Intestinal Ulcerogenic Response To Imc In mentioning

confidence: 99%

“…It is noteworthy that changes in the biological characteristics of AA rats correspond to those that occur in human RA. 3,5,6,38,39) Therefore, AA rats may provide a useful model for studies on the mechanisms of NSAIDs-induced gastrointestinal lesions in RA. It is known that the severity of arthritis in Wistar rats is moderate and occurs with an incidence of only 50-60%.…”

Section: Gastric and Small Intestinal Ulcerogenic Response To Imc In mentioning

confidence: 99%

Effect of Solid Nanoparticle of Indomethacin on Therapy for Rheumatoid Arthritis in Adjuvant-Induced Arthritis Rat

Nagai

Ito

2014

Biological & Pharmaceutical Bulletin

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We designed new oral formulations containing indomethacin (IMC) solid nanoparticles, and investigate their usefulness by evaluating bioavailability and gastrointestinal lesions. The IMC solid nanoparticles were prepared using methylcellulose (MC), 2-hydroxypropyl-β-cyclodextrin (HPβCD), and the bead mill method, and high quality dispersions containing 1.0% IMC nanoparticles were prepared (IMC nano , particle size: 76 58 nm, means S.D.). The fate of serum IMC and the induction of paw edema in adjuvant-induced arthritis (AA) rats receiving low-doses IMC nano (0.4 mg/kg) were similar to those following the administration of a therapeutic dose of conventional IMC prepared with MC and HPβCD (conventional IMC, 2 mg/kg), and the bioavailability in 0.4 mg/kg IMC nano was 5.3-fold higher in comparison with that in 2 mg/kg conventional IMC. IMC-induced gastrointestinal lesions in AA rats administered IMC nano (8 mg/kg), in consideration of bioavailability, were significantly less than for conventional IMC (40 mg/kg). On the other hand, the toxicity caused by conventional IMC and IMC nano was similar in Caco-2 cells. It is possible that the oral administration of IMC solid nanoparticles will show increased effectiveness in treating RA without causing IMC-induced gastrointestinal lesions, since the bioavailability is higher than that of conventional IMC. An oral drug delivery system using drug nanoparticles may expand the usage of NSAIDs for therapy in the inflammatory field.

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Rat models of arthritis: Similarities, differences, advantages, and disadvantages in the identification of novel therapeutics

Schopf¹,

Anderson²,

Jaffee³

2006

In Vivo Models of Inflammation

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FK506 is superior to methotrexate in therapeutic effects on advanced stage of rat adjuvant-induced arthritis

Abstract: The results show that FK506 is more effective and less toxic than MTX in treating established AIA in rats.

Cited by 47 publications

References 24 publications

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

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

Effect of Solid Nanoparticle of Indomethacin on Therapy for Rheumatoid Arthritis in Adjuvant-Induced Arthritis Rat

Rat models of arthritis: Similarities, differences, advantages, and disadvantages in the identification of novel therapeutics

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