Combined gemfibrozil (peroxisome proliferator-activated receptor alpha agonist) with reduced steroid dose gives a similar management picture as the full steroid dose in a rat adjuvant-induced arthritis model

Abstract

Objectives: The study aimed to evaluate the efficacy of combined gemfibrozil with prednisolone in the management of adjuvant-induced arthritis (AIA) rat model.Methods: Seventy two adult male Wistar albino rats were divided equally into 1-control group, three diseased groups: 2- Adjuvant induced arthritis (AIA), 3- high fat diet (HF), and 4- combined AIA-HF, and treated groups: 5- gemfibrozil 30 mg/kg treated AIA group (AIA-G) and the combined AIA-HF treated groups: 6- prednisolone equivalent to human 10 mg (AIA-HF-P10), 7- prednisolone equivalent to human 5 mg (AIA-HF-P5) 8- gemfibrozil (HF-AIA-G) and 9- combined treatment (HF-AIA-G-P5)Results: HF diet represents a precipitating factor for knee arthritis. Gemfibrozil improved the inflammatory findings in both AIA and AIA-HF groups. Combined administration of gemfibrozil with reduced steroid dose gave a similar therapeutic effect to the full steroid dose. Fortunately, we reported more reduction in the nuclear factor kappa-B (NF-κB) and high mobility group box 1 (HMGB1) in the HF-AIA-G-P5 compared with the HF-AIA-P10 group. The improvement was proved by the histological findings.Conclusion: Combined reduced prednisolone dose with gemfibrozil potentiates its anti-inflammatory activity. This could be a target in the management of rheumatoid arthritis.