Abstract | INTRODUCTION: METHODS: Initially, 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. RESULTS: In 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. CONCLUSIONS: The 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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Authors | Liam G Coulthard, Jaclyn Costello, Brent Robinson, Ian A Shiels, Stephen M Taylor, Trent M Woodruff |
Journal | Arthritis research & therapy
(Arthritis Res Ther)
Vol. 13
Issue 2
Pg. R42
(Mar 14 2011)
ISSN: 1478-6362 [Electronic] England |
PMID | 21401925
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents
- Enzyme Inhibitors
- Phospholipases A2, Secretory
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Topics |
- Animals
- Anti-Inflammatory Agents
(pharmacology)
- Arthritis, Experimental
(drug therapy, pathology)
- Disease Models, Animal
- Enzyme Inhibitors
(pharmacology)
- Enzyme-Linked Immunosorbent Assay
- Female
- Phospholipases A2, Secretory
(antagonists & inhibitors)
- Rats
- Rats, Wistar
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