ArticleArthritis research & therapy2011
Comparative efficacy of a secretory phospholipase A2 inhibitor with conventional anti-inflammatory agents in a rat model of antigen-induced arthritis.
Article in Arthritis research & therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 21 citations in OpenAlex.
- Multimodal regulation of the osteoclastogenesis process by secreted group IIA phospholipase AFrontiers in cell and developmental biology · 2022Article
- Phospholipase AScience advances · 2021Article
- LncRNAs and Rheumatoid Arthritis: From Identifying Mechanisms to Clinical Investigation.Frontiers in immunology · 2021Review
- Skeletal muscle redox signaling in rheumatoid arthritis.Clinical science (London, England : 1979) · 2020Review
- Selective inhibition of CDK7 ameliorates experimental arthritis in mice.Clinical and experimental medicine · 2015Article
- AMPA/kainate glutamate receptors contribute to inflammation, degeneration and pain related behaviour in inflammatory stages of arthritis.Annals of the rheumatic diseases · 2015Article
- Nimesulide improves the symptomatic and disease modifying effects of leflunomide in collagen induced arthritis.PloS one · 2014Article
- Response to 'Ramipril attenuates lipid peroxidation and cardiac fibrosis in an experimental model of rheumatoid arthritis' - authors' reply.Arthritis research & therapy · 2013Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionPreviously, secretory phospholipase A2 (sPLA2) inhibition has been used as an adjunct to conventional rheumatoid arthritis therapy in human clinical trials without significant improvement of arthritic pathology. In this study, we compared the efficacy of a potent and orally active group IIa secretory phospholipase A2 inhibitor (sPLA2I) to conventional anti-arthritic agents; infliximab, leflunomide and prednisolone, in a rat model of antigen-induced arthritis.
methodsInitially, to establish efficacy and dose-response, rats were orally dosed with the sPLA2I (1 and 5 mg/kg) two days prior to arthritis induction, and then daily throughout the 14-day study period. In the second trial, rats were orally dosed with the sPLA2I (5 and 10 mg/kg/day) beginning two days after the induction of arthritis, at the peak of joint swelling. Separate groups of rats were also dosed with the tumour necrosis factor-alpha (TNF-α) inhibitor infliximab (single 3 mg/kg i.v. injection), leflunomide (10 mg/kg/day, oral) or prednisolone (1 mg/kg/day, oral) at this same time point and used as comparative treatments.
resultsIn the pathology prevention trial, both 1 and 5 mg/kg dose groups of sPLA2I demonstrated a significant reduction in joint swelling and gait disturbances; however, only the higher 5 mg/kg dose resulted in significantly reduced histopathology scores. In the post-induction trial, rats dosed with sPLA2I showed a significant improvement in joint swelling and gait scoring, whereas none of the conventional therapeutics achieved a significant decrease in both of these two disease markers. Histopathological scoring at the end-point of the study demonstrated significantly reduced median scores in rats treated with 10 mg/kg sPLA2I and leflunomide.
conclusionsThe results from this study suggest a pathogenic role for sPLA2 enzymes in this model of arthritis in rats, and the potential clinical utility of sPLA2 inhibition as a safer, and more effective, alternative to conventional anti-arthritic therapeutics.
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