Tranilast Suppresses the Disease Development of the Adjuvant- and Streptococcal Cell Wall-Induced Arthritis in Rats

Nagate, Toshiaki; Tamura, Toru; Sato, Fumiyasu; Kuroda, Junji; Nakayama, Jun; Shibata, Nobuhiko

doi:10.1254/jphs.fp0070534

Cited by 15 publications

(17 citation statements)

References 27 publications

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“…14,52) In this study, paw edema of the right hind feet of AA rats treated with the TL micro gel ointment was significantly decreased (Table 4, Fig. 8).…”

Section: Discussionsupporting

confidence: 50%

“…13) Recently, it was reported that TL suppresses the development of RA in multiple models, and TL is expected to become a novel therapeutic agent for human RA. 14) Despite its positive pharmacological effects on inflammatory diseases, TL exhibits poor dissolution behavior and poor solubility (14.5 µg/mL in water), particularly under acidic conditions (0.7 µg/mL in buffer solution of pH 1.2), 15) so that the daily dose of TL must be relatively high (300 mg/d). Therefore, the oral administration of TL is often limited due to systemic side effects that include liver dysfunction, abdominal discomfort, skin rash, and allergic cystitis.…”

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confidence: 99%

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Therapeutic Effects of Gel Ointments Containing Tranilast Nanoparticles on Paw Edema in Adjuvant-Induced Arthritis Rats

Nagai

Ito

2014

Biological & Pharmaceutical Bulletin

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Tranilast (TL), an antiallergic agent, has been clinically used in the treatment of bronchial asthma, although its clinical use has been limited by its poor solubility in water, photodegradation and systemic side effects. In this study, we prepared a gel ointment containing TL nanoparticles (TL nano gel ointment), and investigated its usefulness. In addition, we demonstrated the preventive effects of the TL nano gel ointment on inflammation in adjuvant-induced arthritis (AA) rats. The TL nano gel ointment was prepared using Bead Smash 12 (a bead mill) and additives including sodium docusate, 2-hydroxypropyl-β-cyclodextrin, methylcellulose and Carbopol 934; the mean particle diameter of the TL nanoparticles was 71.0 25.4 nm. In in vitro skin penetration experiments, the amount of penetrated TL, the penetration rate (J c ) and the penetration coefficient through the skin (K p ) of the TL nano gel ointment were significantly higher than those of a gel ointment containing TL microparticles (TL micro gel ointment; particle diameter 50.5 26.3 µm). The TL concentrations in the skin tissue and plasma of rats receiving the TL nano gel ointment were also higher than in rats receiving the TL micro gel ointment. In addition, the application of the TL nano gel ointment attenuated the increase in paw edema of the hind feet of AA rats in comparison with AA rats treated with the TL micro gel ointment. These results suggest that TL nanoparticles can be applied to the formulation of a transdermal system, and that a transdermal formulation using TL nanoparticles might be a delivery option for the clinical treatment of RA.

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“…14,52) In this study, paw edema of the right hind feet of AA rats treated with the TL micro gel ointment was significantly decreased (Table 4, Fig. 8).…”

Section: Discussionsupporting

confidence: 50%

mentioning

confidence: 99%

Therapeutic Effects of Gel Ointments Containing Tranilast Nanoparticles on Paw Edema in Adjuvant-Induced Arthritis Rats

Nagai

Ito

2014

Biological & Pharmaceutical Bulletin

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“…Disease suppression was seen both in clinical parameters and histological findings across the whole pathology of arthritis. One of the proposed targets of MTX immune suppression is T cells [10]. As the pathology of SKG mice is dependent on autoreactive T cells presumably by genetic alteration [15], it is reasonable to hypothesize Marked bone erosion and synovial cell hyperplasia can be seen in B, and severe inflammatory cell infiltration can be seen in B1 for the mice in Group 2 (boxed area in B is enlarged as B1).…”

Section: Discussionmentioning

confidence: 99%

“…The H&E-stained preparations were microscopically observed focusing on the distal tibia-talocrural joint. The scoring methods were based on previous reports [10]. Briefly, the sum of a 4-point scoring system (0, no significant changes, 1, mild, 2, moderate, 3, marked) was considered as the histopathological score of each section, and the average score of each group was compared for bone erosion, new bone formation, pannus formation, cartilage destruction, synovial cell hyperplasia, inflammatory cell infiltration, circumarticular fibrosis and edema.…”

Section: Animalsmentioning

confidence: 99%

Therapeutic and Preventive Effects of Methotrexate on Zymosan-Induced Arthritis in SKG Mice

Nagate

Kawai

Nakayama

2009

The Journal of Veterinary Medical Science

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ABSTRACT. The purpose of this study was to investigate the pathology of zymosan-induced arthritis in the SKG mouse model of rheumatoid arthritis in humans, and to validate this model as a reliable drug screening system. To achieve this purpose, methotrexate (1 or 10 mg/kg, once daily) or vehicle only was administered intraperitoneally to SKG mice with zymosan-induced arthritis. Histologically, this arthritis was characterized by the presence of granulation tissue rich in granulocytes. Methotrexate suppressed the development of arthritis in ankle and wrist joints in both clinical and histological studies. These results indicated that methotrexate has not only prophylactic, but also therapeutic effects on zymosan-induced arthritis developed in SKG mice and may thus be a promising control agent for drug research in the SKG mouse model of rheumatoid arthritis.

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“…In arthritis research, the most common model systems are rodents like rats or mice. 1,2 Using animal models offer advantages like the possibility to observe systemic physiological effects by pharmaceutical agents. However, animal models also possess disadvantages.…”

Section: Introductionmentioning

confidence: 99%

Tissue‐engineered cartilage of porcine and human origin as in vitro test system in arthritis research

Göhring

Lübke

Andreas

et al. 2010

Biotechnology Progress

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The increasing prevalence of cartilage destruction during arthritis has entailed an intensified amount for in vitro cartilage models to analyze pathophysiological processes and to screen for antirheumatic drugs. Tissue engineering offers the opportunity to establish highly organized 3D cell cultures facilitating the formation of in vitro models that reflect the human situation. We report the comparison of porcine chondrocyte pellet and alginate bead cultures as model systems for human cartilage and the further development into a human system that was applied in an arthritis model. In porcine pellet and alginate cultures, formation of cartilage matrix similar to human matrix was verified by histology and PCR. As alginate beads could be cultivated batch-wise in one well of a multiwell plate, we further developed this setting into a human system. In contrast, each pellet had to be cultivated individually in one well of a multiwell plate, which is time consuming. Following stimulation of human chondrocyte alginate cultures with conditioned media from human synovial fibroblasts derived from arthritis patients, microarray analysis verified the induction of genes related to cartilage destruction (like MMP10, -12) and inflammation (like IL6, -8 and chemokines). Several genes are coding for proteins that are members of inflammatory and catabolic pathways. Belonging to the most affected pathways, we identified the focal adhesion, cytokine-cytokine receptor interaction, ECM-receptor signalling, Jak-STAT signalling, and toll-like receptor signalling pathways, all relevant in arthritis. Therefore, we demonstrate that engineered cartilage of porcine and human origin represents a powerful in vitro model for cartilage in vivo.

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Tranilast Suppresses the Disease Development of the Adjuvant- and Streptococcal Cell Wall-Induced Arthritis in Rats

Cited by 15 publications

References 27 publications

Therapeutic Effects of Gel Ointments Containing Tranilast Nanoparticles on Paw Edema in Adjuvant-Induced Arthritis Rats

Therapeutic Effects of Gel Ointments Containing Tranilast Nanoparticles on Paw Edema in Adjuvant-Induced Arthritis Rats

Therapeutic and Preventive Effects of Methotrexate on Zymosan-Induced Arthritis in SKG Mice

Tissue‐engineered cartilage of porcine and human origin as in vitro test system in arthritis research

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