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Nimesulide improves the symptomatic and disease modifying effects of leflunomide in collagen induced arthritis.

Al-Abd AM, Al-Abbasi FA, Nofal SM, Khalifa AE, Williams RO, El-Eraky WI, Nagy AA, Abdel-Naim AB - PLoS ONE (2014)

Bottom Line: Nimesulide induced only transient symptomatic alleviation on the top of decreased leucocytic infiltration compared to arthritis group.However, nimesulide alone failed to induce any significant improvement in the radiological or pathological disease progression.Combination of nimesulide and leflunomide significantly improved symptomatic (analgesia and joint stiffness) and arthritic disease progression (radiological, pathological and Myeloperoxidase enzyme activity) in collagen induced arthritis animal model.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.

ABSTRACT
Nimesulide is a COX-2 inhibitor used for symptomatic relief of rheumatoid arthritis. Leflunomide is an anti-pyrimidine used to manage the progression of rheumatoid arthritis. Herein we studied the influence of nimesulide and leflunomide combination in terms of disease symptoms and progression using collagen-induced arthritis model in mice, as a model for rheumatoid arthritis. Collagen induced arthritis was induced by immunization with type II collagen. Assessment of joint stiffness and articular hyperalgesia were evaluated using a locomotor activity cage and the Hargreaves method, respectively. Disease progression was assessed via arthritic index scoring, X-ray imaging, myeloperoxidase enzyme activity and histopathologic examination. Nimesulide induced only transient symptomatic alleviation on the top of decreased leucocytic infiltration compared to arthritis group. However, nimesulide alone failed to induce any significant improvement in the radiological or pathological disease progression. Leflunomide alone moderately alleviates the symptoms of arthritis and moderately retarded the radiological and pathological disease progression. Combination of nimesulide and leflunomide significantly improved symptomatic (analgesia and joint stiffness) and arthritic disease progression (radiological, pathological and Myeloperoxidase enzyme activity) in collagen induced arthritis animal model.

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Assessment of disease progression.Mice with CIA were treated with leflunomide (LEF: ▪), nimesulide (NIM: □), or leflunomide+nimesulide (LEF+NIM: ▴) and compared to untreated arthritic (○) and normal mice (•). Arthritic index (AI) of mice was recorded over the duration of 40 days (A). Hind paws of mice were x-ray imaged at day 40 (B) and given a radiological score (C) as shown in the methods section. Data are presented as mean ± SD. ** Significantly different from CIA-mice.
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pone-0111843-g002: Assessment of disease progression.Mice with CIA were treated with leflunomide (LEF: ▪), nimesulide (NIM: □), or leflunomide+nimesulide (LEF+NIM: ▴) and compared to untreated arthritic (○) and normal mice (•). Arthritic index (AI) of mice was recorded over the duration of 40 days (A). Hind paws of mice were x-ray imaged at day 40 (B) and given a radiological score (C) as shown in the methods section. Data are presented as mean ± SD. ** Significantly different from CIA-mice.

Mentions: Arthritic index (AI) is a semi quantitative parameter that reflecting the severity of polyarthritis. Animals showed stable, low grade, and persistent polyarthritis after immunization with collagen. Animals treated with leflunomide+nemisulide showed the fastest onset of improvement in AI (31 days after the primary induction of arthritis). Animals treated with leflunomide or nimesulide alone started to show improvement in AI at day 35 after induction. After 40 days of induction, the reduction in AI scores was found to be 31.4%, 22.3%, and 43.8% in LEF-group, NIM-group, and (LEF+NIM)-group respectively compared to the CIA controlgroup Fig. 2-A.


Nimesulide improves the symptomatic and disease modifying effects of leflunomide in collagen induced arthritis.

Al-Abd AM, Al-Abbasi FA, Nofal SM, Khalifa AE, Williams RO, El-Eraky WI, Nagy AA, Abdel-Naim AB - PLoS ONE (2014)

Assessment of disease progression.Mice with CIA were treated with leflunomide (LEF: ▪), nimesulide (NIM: □), or leflunomide+nimesulide (LEF+NIM: ▴) and compared to untreated arthritic (○) and normal mice (•). Arthritic index (AI) of mice was recorded over the duration of 40 days (A). Hind paws of mice were x-ray imaged at day 40 (B) and given a radiological score (C) as shown in the methods section. Data are presented as mean ± SD. ** Significantly different from CIA-mice.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4222915&req=5

pone-0111843-g002: Assessment of disease progression.Mice with CIA were treated with leflunomide (LEF: ▪), nimesulide (NIM: □), or leflunomide+nimesulide (LEF+NIM: ▴) and compared to untreated arthritic (○) and normal mice (•). Arthritic index (AI) of mice was recorded over the duration of 40 days (A). Hind paws of mice were x-ray imaged at day 40 (B) and given a radiological score (C) as shown in the methods section. Data are presented as mean ± SD. ** Significantly different from CIA-mice.
Mentions: Arthritic index (AI) is a semi quantitative parameter that reflecting the severity of polyarthritis. Animals showed stable, low grade, and persistent polyarthritis after immunization with collagen. Animals treated with leflunomide+nemisulide showed the fastest onset of improvement in AI (31 days after the primary induction of arthritis). Animals treated with leflunomide or nimesulide alone started to show improvement in AI at day 35 after induction. After 40 days of induction, the reduction in AI scores was found to be 31.4%, 22.3%, and 43.8% in LEF-group, NIM-group, and (LEF+NIM)-group respectively compared to the CIA controlgroup Fig. 2-A.

Bottom Line: Nimesulide induced only transient symptomatic alleviation on the top of decreased leucocytic infiltration compared to arthritis group.However, nimesulide alone failed to induce any significant improvement in the radiological or pathological disease progression.Combination of nimesulide and leflunomide significantly improved symptomatic (analgesia and joint stiffness) and arthritic disease progression (radiological, pathological and Myeloperoxidase enzyme activity) in collagen induced arthritis animal model.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.

ABSTRACT
Nimesulide is a COX-2 inhibitor used for symptomatic relief of rheumatoid arthritis. Leflunomide is an anti-pyrimidine used to manage the progression of rheumatoid arthritis. Herein we studied the influence of nimesulide and leflunomide combination in terms of disease symptoms and progression using collagen-induced arthritis model in mice, as a model for rheumatoid arthritis. Collagen induced arthritis was induced by immunization with type II collagen. Assessment of joint stiffness and articular hyperalgesia were evaluated using a locomotor activity cage and the Hargreaves method, respectively. Disease progression was assessed via arthritic index scoring, X-ray imaging, myeloperoxidase enzyme activity and histopathologic examination. Nimesulide induced only transient symptomatic alleviation on the top of decreased leucocytic infiltration compared to arthritis group. However, nimesulide alone failed to induce any significant improvement in the radiological or pathological disease progression. Leflunomide alone moderately alleviates the symptoms of arthritis and moderately retarded the radiological and pathological disease progression. Combination of nimesulide and leflunomide significantly improved symptomatic (analgesia and joint stiffness) and arthritic disease progression (radiological, pathological and Myeloperoxidase enzyme activity) in collagen induced arthritis animal model.

Show MeSH
Related in: MedlinePlus