RESUMEN
The type II collagen-induced arthritis (CIA) model and human rheumatoid arthritis exhibit similar characteristics. Both diseases involve the production of inflammatory cytokines and other mediators, triggering an inflammatory cascade linked to bone and cartilage damage. Recently, new pyrazole compounds with various pharmacological activities, including antimicrobial, anticancer, anti-inflammatory, and analgesic agents, have been reported. Our aim is to evaluate the therapeutic effectiveness of two newly synthesized pyrazole derivatives, M1E and M1G, in reducing inflammation and oxidative stress in a mouse model of collagen-induced arthritis. Arthritis was induced in DBA/1J mice, and the therapeutic effect of the M1E and M1G is assessed by measuring the arthritic index, quantifying the expression of inflammatory genes such as p38 MAPK, COX-2, IL1ß, MMP3, and TNF-α using real-time PCR and analyzing protein expression using western blotting for phosphorylated p38 MAPK and COX-2. Oxidative stress markers and hind paws joint histopathology were also evaluated. Treatment with the two pyrazole derivatives significantly (p < 0.001) improved the arthritic score; downregulated the expression of inflammatory genes p38 MAPK, COX-2, IL1ß, MMP3, and TNF-α; and reduced the protein expression of phosphorylated p3 MAPK and COX-2. In addition, both compounds ameliorated oxidative stress by increasing the activities of SOD and reducing the formation of MDA in the paw tissue homogenates. Both M1E and M1G significantly (p < 0.001) improved the pathological features of synovitis. The pyrazole derivatives, M1E and M1G, significantly reduced the arthritic score and the inflammatory cytokine expression, improved synovitis histopathology, and ameliorated oxidative stress in the CIA mice model.
RESUMEN
Knee osteoarthritis (OA) is a common disabling disease. Epidemiological studies have revealed various risk factors for OA, including sex, aging, obesity, occupational illnesses, and chronic diseases. Here we evaluate the clinical, pathological, and radiological findings of knee OA in a subset of Saudi patients who were subjected to total knee replacement (TKA). The study population included 30 Saudi patients with knee OA who were operated by TKA (from June 2014 to December 2015) in the Department of Orthopedics, Faculty of Medicine, King Abdulaziz University, Saudi Arabia. Patient's clinical and radiological data were collected from the hospital files. Pathological examination of the excised superior articular surface of tibia and femoral condyles were done. Pearson Chi-squared analysis was used to test for differences between the variables in associated risk factors. There were more women than men. Sixty per cent of patients were older than 60 years [mean age, 59.2 (females) and 61.7 (men) years-old]. All patients exceeded obesity class 1, with females being more obese than males. Pathological examination of the superior articular surface of tibia and femoral condyles showed high score lesions, which was more apparent in females than in males. Radiological findings showed that most lesions were high grade. The findings of this study will help to understand the pathogenesis of OA and improve treatment decision making relevant to TKA in knee OA in Saudi Arabia and elsewhere.
La artrosis de rodilla (OA, por sus siglas en inglés) es una enfermedad invalidante común. Los estudios epidemiológicos han revelado diversos factores de riesgo para la OA, que incluyen el sexo, el envejecimiento, la obesidad, las enfermedades profesionales y las enfermedades crónicas. Aquí evaluamos los hallazgos clínicos, patológicos y radiológicos de la OA de rodilla en un subconjunto de pacientes sauditas que fueron sometidos a reemplazo total de rodilla (RTR). La población de estudio incluyó a 30 pacientes saudíes con OA de rodilla que fueron operados por RTR (desde junio de 2014 hasta diciembre de 2015) en el Departamento de Ortopedia, Facultad de Medicina, King Abdulaziz University, Arabia Saudita. Los datos clínicos y radiológicos de los pacientes se obtuvieron de las fichas hospitalarias. Se realizó examen patológico de la superficie articular superior de la tibia extirpada y cóndilos femorales. Se utilizó el análisis Chi-cuadrado de Pearson para probar las diferencias entre las variables en los factores de riesgo asociados. El número de mujeres era mayor que los hombres. El 60 % de los pacientes eran mayores de 60 años [edad media, 59,2 (mujeres) y 61,7 (hombres) años]. Todos los pacientes superaron la obesidad clase 1, siendo las mujeres más obesas que los hombres. El examen patológico de la superficie articular superior de la tibia y los cóndilos femorales mostraron lesiones con puntaje alto, que fue más evidente en mujeres que en hombres. Los hallazgos radiológicos mostraron que la mayoría de las lesiones eran de alto grado. Los hallazgos de este estudio ayudarán a comprender la patogenia de la OA y mejorarán la toma de decisiones sobre el tratamiento relevante para el RTR en la OA de rodilla en Arabia Saudita y en otros lugares.