EXPERIMENTAL MODEL OF SYSTEMIC INFLAMMATION DURING ACETAMINOPHEN TOXICITY

Abstract

Introduction. Acetaminophen (paracetamol) is one of the most common analgesic and antipyretic agents, which is why overdoses with this drug often occur, associated with acute hepatotoxicity and systemic inflammation, worsening the prognosis for the patient. In this case, systemic inflammation is characterised by systemic activation of the immune system. However, the contribution of different types of immune cells to the pathogenesis of acetaminophen poisoning has not been sufficiently studied which determined the purpose of this work. The aim of this work was to evaluate changes in the number of cells expressing CD3⁺, CD20⁺, CD45⁺ in organ of C57Bl/6 mice during acute acetaminophen poisoning. Materials and methods. The study was performed on sexually mature male C57Bl/6 mice. The mice were divided into 2 groups of 7 mice in each group. The experimental group included animals administered acetaminophen solution (Sigma-Aldrich, USA) at a dose of 600 mg/kg at a concentration of 14 mg/ml. An equivalent volume of physiological solution was administered to the control group. The animals were taken out of the experiment after 24 hours and internal organs were removed. Primary rabbit antibodies from Sigma-Aldrich (C7930), Thermo Fisher Scientific (PA5-16701), Abcam (ab281586) were used for immunohistochemical study for CD3⁺, CD20⁺, CD45⁺. Secondary antibodies were taken from Thermo Fisher Scientific (31820). Results. When assessing the content of CD20⁺ cells in organ tissues of C57Bl/6 mice, single cells in the field of view were observed. Statistically significant differences were not revealed by Mann-Whitney U-criterion, which indicates the absence of B-lymphocytes contribution to the pathogenesis of acetaminophen poisoning in the first 24 hours. A statistically significant decrease in the number of CD3⁺ cells in heart tissue was determined. 24 hours after the toxicant administration, an increase in the number of CD45⁺ expressing immune cells in the liver, mainly due to segmented neutrophils, was noted. Conclusions. Thus, in the first day after acute acetaminophen poisoning in experimental animals there is no significant change of CD3⁺ and CD20⁺ expressing cells in tissues. At the same time there is an increase in the content of immune cells to the liver tissue, mainly due to neutrophils.