Experimental Study of Aspects of Therapeutic Action of New Derivative of Oxaminic Acid

Some aspects of the mechanism of the anti-inflammatory action of oxaminic acid such as metoxarade during chronic inflammatory process were studied. The purpose of the investigation was to elicit the mechanism of the anti-inflammatory action of metoxarade, to study its influence on the chronic process which is close to the pathogenesis and morphofunctional changes to the connective tissue disease (collagenoses). The specific activity of metoxarade according to the Methodical recommendations on experimental (preclinical) research of NSAIDs was being studied. Metoxarade is a white powder with a melting point of 203-205 ° C, soluble in DMF and sparingly soluble in water. This compound has been synthesized at the Department of Pharmaceutical Analysis of the National University of Pharmacy. As a model of collagenoses the adjuvant disease has been used, in the pathogenesis of which there is a reaction of hypersensitivity of the delayed type and autoimmune mechanisms with preferentially localized disease process in joints and myocardium. The study of the effect of metoxarade on chronic inflammation has been performed on the adjuvant arthritis model in white rats. Therapeutic and prophylactic effect of metoxarade was assessed due to its ability to reduce the swelling of the foot, secondary inflammatory changes, perimeter of the tail and to normalize the following hematological parameters: erythrocyte sedimentation rate (ESR), a change in leukocyte counts, the ability to prevent destructive changes in the connective tissue of the knee and ankle joints, as well as to reduce the dystrophic changes in the myocardium. These parameters of anti-inflammatory activity were recorded at the beginning and the end of the experiment. During the experiment, the volume of feet, body weight and level of secondary inflammatory lesions (the level of inflammation of ears, forelegs, left hind foot) were being registered. The volume of the affected foot was measured by oncometric method. Hematological parameters were recorded three times: the original background, on the 14th and 28th day. Indicators of clinical blood count were determined due to conventional techniques. The introduction of Freund's adjuvant caused polyarthritis joint damage in rats and changes of hematological parameters in experimental animals (pronounced leukocytosis, accelerated ESR), and led to the emergence of gross destructive and dystrophic disorders of the joints, the development of degenerative changes of the myocardium and disturbance of microcirculation. Received results indicated high anti-inflammatory activity of metoxarade: adhesion prevents the development of systemic joint's damage, decreased the percent of destructive changes in the joints, and promoted the process of restorative regeneration of damaged muscular cells of the heart by experimental adjuvant disease. In animals which received metoxarade in the dose of 39,8 mg/kg, it prevented the presence secondary signs of exudation and also there were absent signs of arthritis of forelegs and hind feet. Metoxarade normalized hematological indices of rats, increased the time of blood coagulation on 25,5%. Metoxarade's intake was tolerated by animals well, significant changes in general condition and animal's behavior in experiments were not determined. It is necessary and important to study the action of metoxarade in order to create new medicinal agent with anti-inflammatory and antiexudative peculiarities.