Ameliorative Effect of Dabigatran on CFA-Induced Rheumatoid Arthritis via Modulating Kallikrein-Kinin System in Rats
Rheumatoid arthritis is an autoimmune disease that affects joints, leading to swelling, inflammation, and dysfunction in the joints. Recently, research efforts have been focused on finding novel curative approaches for rheumatoid arthritis, as current therapies are associated with adverse effects. Here, we examined the effectiveness of dabigatran, the antithrombotic agent, in treating complete Freund's adjuvant (CFA)-induced arthritis in rats. Subcutaneous injection of a single 0.3 mL dosage of CFA into the rat's hind leg planter surface resulted in articular surface deformities, reduced cartilage thickness, loss of intercellular matrix, and inflammatory cell infiltration. There were also increased levels of the Anti-cyclic citrullinated peptide antibody (ACPA), oxidative stress, and tissue Receptor activator of nuclear factor-kappa B ligand (RANKL). Proteins of the kallikrein-kinin system (KKS) were also elevated. The inhibitory effects of dabigatran on thrombin led to a subsequent inhibition of KKS and reduced Toll-like receptor 4 (TLR4) expression. These effects also decreased RANKL levels and showed anti-inflammatory and antioxidant effects. Therefore, dabigatran could be a novel therapeutic strategy for arthritis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
International journal of molecular sciences - 23(2022), 18 vom: 07. Sept. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Youssef, Mahmoud E [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.09.2022 Date Revised 28.09.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/ijms231810297 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 245 | 1 | 0 | |a Ameliorative Effect of Dabigatran on CFA-Induced Rheumatoid Arthritis via Modulating Kallikrein-Kinin System in Rats |
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| 520 | |a Rheumatoid arthritis is an autoimmune disease that affects joints, leading to swelling, inflammation, and dysfunction in the joints. Recently, research efforts have been focused on finding novel curative approaches for rheumatoid arthritis, as current therapies are associated with adverse effects. Here, we examined the effectiveness of dabigatran, the antithrombotic agent, in treating complete Freund's adjuvant (CFA)-induced arthritis in rats. Subcutaneous injection of a single 0.3 mL dosage of CFA into the rat's hind leg planter surface resulted in articular surface deformities, reduced cartilage thickness, loss of intercellular matrix, and inflammatory cell infiltration. There were also increased levels of the Anti-cyclic citrullinated peptide antibody (ACPA), oxidative stress, and tissue Receptor activator of nuclear factor-kappa B ligand (RANKL). Proteins of the kallikrein-kinin system (KKS) were also elevated. The inhibitory effects of dabigatran on thrombin led to a subsequent inhibition of KKS and reduced Toll-like receptor 4 (TLR4) expression. These effects also decreased RANKL levels and showed anti-inflammatory and antioxidant effects. Therefore, dabigatran could be a novel therapeutic strategy for arthritis | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Abdel-Reheim, Mustafa A |e verfasserin |4 aut | |
| 700 | 1 | |a Morsy, Mohamed A |e verfasserin |4 aut | |
| 700 | 1 | |a El-Daly, Mahmoud |e verfasserin |4 aut | |
| 700 | 1 | |a Atwa, Gamal M K |e verfasserin |4 aut | |
| 700 | 1 | |a Yahya, Galal |e verfasserin |4 aut | |
| 700 | 1 | |a Cavalu, Simona |e verfasserin |4 aut | |
| 700 | 1 | |a Saber, Sameh |e verfasserin |4 aut | |
| 700 | 1 | |a Ahmed Gaafar, Ahmed Gaafar |e verfasserin |4 aut | |
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