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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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Histopathological assessment of articular damage.Mice with CIA were treated with leflunomide (LEF: Panel C), nimesulide (NIM: Panel D), or leflunomide+nimesulide (LEF+NIM: Panel E) for 40 days and the H&E stained joints were compared with untreated arthritic (CIA: Panel B) and normal mice (Panel A). Pathological findings were compared in terms of synovial hyperplasia (S), articular irregularity (A), narrowing of joint space (N), and lymphocytic infiltration (M).
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pone-0111843-g003: Histopathological assessment of articular damage.Mice with CIA were treated with leflunomide (LEF: Panel C), nimesulide (NIM: Panel D), or leflunomide+nimesulide (LEF+NIM: Panel E) for 40 days and the H&E stained joints were compared with untreated arthritic (CIA: Panel B) and normal mice (Panel A). Pathological findings were compared in terms of synovial hyperplasia (S), articular irregularity (A), narrowing of joint space (N), and lymphocytic infiltration (M).

Mentions: Articular damage was further confirmed pathologically in H&E stained sagittal sections in the joints of mice. CIA resulted in severe hyperplasia in the synovial membrane, irregularity and roughness of the articular surface, and narrowing of joint space as well as excessive leucocytic infiltration Fig. 3-A&B. Treatment with nimesulide alone resulted in decreased intra-articular leucocytic infiltration Fig. 3-D. Synovial membrane hyperplasia, articular surface roughness and narrowing of the joint space were decreased by leflunomide treatment Fig. 3-C. Of all the treatment groups, leflunomide+nimesulide showed the greatest histopathological improvement compared to the CIA group Fig. 3-E.


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)

Histopathological assessment of articular damage.Mice with CIA were treated with leflunomide (LEF: Panel C), nimesulide (NIM: Panel D), or leflunomide+nimesulide (LEF+NIM: Panel E) for 40 days and the H&E stained joints were compared with untreated arthritic (CIA: Panel B) and normal mice (Panel A). Pathological findings were compared in terms of synovial hyperplasia (S), articular irregularity (A), narrowing of joint space (N), and lymphocytic infiltration (M).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0111843-g003: Histopathological assessment of articular damage.Mice with CIA were treated with leflunomide (LEF: Panel C), nimesulide (NIM: Panel D), or leflunomide+nimesulide (LEF+NIM: Panel E) for 40 days and the H&E stained joints were compared with untreated arthritic (CIA: Panel B) and normal mice (Panel A). Pathological findings were compared in terms of synovial hyperplasia (S), articular irregularity (A), narrowing of joint space (N), and lymphocytic infiltration (M).
Mentions: Articular damage was further confirmed pathologically in H&E stained sagittal sections in the joints of mice. CIA resulted in severe hyperplasia in the synovial membrane, irregularity and roughness of the articular surface, and narrowing of joint space as well as excessive leucocytic infiltration Fig. 3-A&B. Treatment with nimesulide alone resulted in decreased intra-articular leucocytic infiltration Fig. 3-D. Synovial membrane hyperplasia, articular surface roughness and narrowing of the joint space were decreased by leflunomide treatment Fig. 3-C. Of all the treatment groups, leflunomide+nimesulide showed the greatest histopathological improvement compared to the CIA group Fig. 3-E.

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