Evaluation of the effect of losartan and methotrexate combined therapy in adjuvant-induced arthritis in rats

Refaat, Rowaida; Salama, Mona; Meguid, E A; Sarha, Ashgan El; Gowayed, Mennatallah A.

doi:10.1016/j.ejphar.2012.10.024

Cited by 51 publications

(34 citation statements)

References 52 publications

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“…showed that losartan and methotrexate combined therapy showed better results than methotrexate and losartan alone. The combined therapy significantly improved paw and liver histopathology, reduced albumin, CRP, nitrite/nitrate concentrations and decreased IL‐1β, TNF‐α, VEGF, aspartate transaminase and alanine transaminase levels . The study showed that losartan increased the efficacy of methotrexate therapy in AA rats with no evidence of toxicity.…”

Section: Ang II and Ramentioning

confidence: 80%

Angiotensin II in inflammation, immunity and rheumatoid arthritis

Cao

Wei

2015

Clinical and Experimental Immunology

101

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SummaryRheumatoid arthritis (RA) is an autoimmune inflammatory disease that is characterized by increased cardiovascular morbidity and mortality, independent of the traditional risk factors for cardiovascular disease. Although classically known for its role in the regulation of circulatory homeostasis, angiotensin II (Ang II) is recognized to act as a powerful proinflammatory mediator. Some research has showed that Ang II plays important roles in autoimmune diseases, including RA, systemic lupus erythematosus and multiple sclerosis. Ang II blockers prove effective in reducing inflammation and autoimmunity in rheumatic diseases and their relative safety, together with their effects for reducing the cardiovascular disease risk, suggest that Ang II blockers may at least act as effective adjunctive therapy for disease control in patients with RA. The present review focuses systematically on the potential impact of Ang II and its receptors on inflammation and immunomodulation in patients with RA.

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Section: Ang II and Ramentioning

confidence: 80%

Angiotensin II in inflammation, immunity and rheumatoid arthritis

Cao

Wei

2015

Clinical and Experimental Immunology

101

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“…Pufe et al . reported that the expression of VEGF protein and receptor is strongly increased in rheumatoid synovium and that the combined therapy of MTX and losartan decreased the level of VEGF in the serum of AIA rats . Given these data, a randomized, placebo‐controlled trial of ARB is warranted to fully evaluate the importance of the angiotensin pathway in RA .…”

Section: Discussionmentioning

confidence: 99%

“…This strongly suggests that a novel therapeutic strategy for RA could be achieved by limiting angiotensin II synthesis or blocking the interaction between angiotensin II and AT1R . Several studies have confirmed the clinical beneficial of ACE inhibitors (ACEIs) and/or AT1R blockers (ARBs) in RA experimental animal models, including AIA and collagen‐induced arthritis .…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II type 2 receptor correlates with therapeutic effects of losartan in rats with adjuvant‐induced arthritis

Wang

Zhu

et al. 2013

J Cellular Molecular Medi

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The angiotensin II type 1 receptor (AT1R) blocker losartan ameliorates rheumatoid arthritis (RA) in an experimental model. In RA, AT2R mainly opposes AT1R, but the mechanism by which this occurs still remains obscure. In the present study, we investigated the role of AT2R in the treatment of rats with adjuvant-induced arthritis (AIA) by losartan. Adjuvant-induced arthritis rats were treated with losartan (5, 10 and 15 mg/kg) and methotrexate (MTX; 0.5 mg/kg) in vivo from day 14 to day 28. Arthritis was evaluated by the arthritis index and histological examination. Angiotensin II, tumour necrosis factor-α, and VEGF levels were examined by ELISA. The expression of AT1R and AT2R was detected by western blot and immunohistochemistry analysis. After stimulation with interleukin-1β in vitro, the effects of the AT2R agonist CGP42112 (10−8–10−5 M) on the chemotaxis of monocytes induced by 10% foetal calf serum (FCS) were analysed by using Transwell assay. Subsequently, the therapeutic effects of CGP42112 (5, 10 and 20 μg/kg) were evaluated in vivo by intra-articular injection in AIA rats. After treatment with losartan, the down-regulation of AT1R expression and up-regulation of AT2R expression in the spleen and synovium of AIA rats correlated positively with reduction in the polyarthritis index. Treatment with CGP42112 inhibited the chemotaxis of AIA monocytes in vitro, possibly because of the up-regulation of AT2R expression. Intra-articular injection with CGP42112 (10 and 20 μg/kg) ameliorated the arthritis index and histological signs of arthritis. In summary, the present study strongly suggests that the up-regulation of AT2R might be an additional mechanism by which losartan exerts its therapeutic effects in AIA rats.

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“…In order to evaluate the progression of AIA, the right hind paw volumes of all animals were measured [19]. This work was started just before FCA injection on day 0 and thereafter continued at every three days till day 28 with a vernier calliper (GBT1214-1986, Shanghai) to measure ankle (tibiotarsal) joint perimeters by an independent observer without prior knowledge of the experimental groups.…”

Section: Methodsmentioning

confidence: 99%

Therapeutic effects of total steroid saponin extracts from the rhizome of Dioscorea zingiberensis C.H.Wright in Freund's complete adjuvant induced arthritis in rats

Zhang¹,

Ito²,

Liang³

et al. 2014

International Immunopharmacology

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The aim of our present study is to explore the anti-arthritic potential effect of total steroid saponins (TSSN) extracted from the rhizome of Dioscorea zingiberensis C.H.Wright (DZW) and to investigate the underlying mechanisms. This work was performed using adjuvant-induced arthritis (AIA) rats in vivo and lipopolysaccharide (LPS) simulated 264.7 macrophage cells in vitro. In AIA-induced arthritic rats, TSSN significantly alleviated the arthritic progression through evaluating arthritic score, immune organ indexes, paw swelling, and body weight. This phenomenon was well correlated with significant suppression of the overproduction of inflammation cytokines (IL-1, IL-1β, IL-6, and TNF-α), oxidant stress makers (MDA and NO), eicosanoids (LTB4 and PGE2), and inflammatory enzymes (5-LOX and COX-2) versus the AIA rats without treatment. On the contrary, the release of SOD and IL-10 was profoundly increased. What’s more, TSSN could obviously ameliorate the translocation of NF-κB to the nucleus through phosphorylation of the p65 and IκBα in vivo and vitro. The current findings demonstrated that TSSN could protect the injured ankle joint from further deterioration and exert its satisfactory anti-arthritis properties through anti-inflammatory and anti-oxidant effects via inactivating NF-κB signal pathway. This research implies that DZW may be a useful therapeutic agent for the treatment of human arthritis.

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Evaluation of the effect of losartan and methotrexate combined therapy in adjuvant-induced arthritis in rats

Cited by 51 publications

References 52 publications

Angiotensin II in inflammation, immunity and rheumatoid arthritis

Angiotensin II in inflammation, immunity and rheumatoid arthritis

Angiotensin II type 2 receptor correlates with therapeutic effects of losartan in rats with adjuvant‐induced arthritis

Therapeutic effects of total steroid saponin extracts from the rhizome of Dioscorea zingiberensis C.H.Wright in Freund's complete adjuvant induced arthritis in rats

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