Фармакокинетика и Фармакодинамика (Mar 2018)
Effect of diclofenac sodium on the level of histamine and serotonin in rats with acute exudative inflammation
Abstract
Problem statement. Diclofenac is considered a well-recognised reference drug in the study of the therapeutic effects and safety of non-steroidal anti-inflammatory drugs. Diclofenac works by inhibiting cyclooxygenase-1 and cyclooxygenase-2. However, no data about the effect of the drug on the level of histamine and serotonin, cellular mediators of inflammation, are available in the literature. The aim of this experimental study is to evaluate the level of histamine and serotonin in rats with acute exudative inflammation and to study the effect of diclofenac sodium on their concentration. Materials and methods. The study was performed in male outbred white rats. Peritonitis induced by intraperitoneal injection of 1 % acetic acid was used as a model of acute exudative inflammation. The concentration of histamine and serotonin in blood plasma and peritoneal exudate was determined by fluorometry. Results. Three hours after the acetic acid injection, the concentration of histamine in the plasma of rats was elevated by a factor of 1.9 (p < 0.05), and the concentration of serotonin was increased threefold (p < 0.05). A single oral dose of 6.3 mg/kg Diclofenac sodium was administered one hour before the onset of inflammation. The test drug significantly reduced histamine levels in the plasma of rats with acute exudative inflammation but had no effect on serotonin levels. Diclofenac sodium did not change the concentration of the inflammatory mediators in the exudate of animals with the experimental pathology. Conclusion. The ability of diclofenac sodium to reduce elevated histamine levels in the plasma of rats with experimental peritonitis may be one of the components of the mechanism by which this drug reduces vascular permeability and swelling.
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