Antioxidant effect evaluation of drugs with different chemical structures by the degree of mast cell degranulation under photodynamic damage

Introduction. This model of skin acute inflammation caused by photodynamic damage (PHD), where reactive oxygen species (ROS) play a key role, enables the analysis of the microcirculation (MCC) dysfunction and degranulation of mast cells (MCs) at the site of exposure. The current study explored the IgE-independent mechanisms of MCs activation caused by PHD and the possibility of its pharmacological correction. Aim of the study – to evaluate the possibilities of using the model of acute inflammation induced by ROS during PHD to study the MCs contribution to the regulation of vascular permeability and to study angioprotective and MCC-improving drugs at the preclinical stage. Materials and methods. Male Wistar rats were injected with a photosensitizer, then anesthetized and laser irradiated 3 hours later, followed by one of the following drugs: hydrocortisone (HC), ethylmethylhydroxypyridine succinate (ES), or quinacrine (QC). Skin MCC was investigated by laser Doppler flowmetry. Calculation and morphometry of MCs was carried out on film preparations of loose connective tissue of the skin. Results. Immediately after PHD, the blood flow in the control group was 1.9 [1.4; 2.3] p. u., which is 55 % less than the initial values. Partial restoration of blood flow up to 3.7 [3.3; 4.0] p.u. was observed after one hour of observation (88 % of baseline, p<0.001). Despite the administration of HC and ES, the blood flow after PHD decreased by 8,5 and 32,5 %, respectively. After an hour, it was only 78 % of the baseline. Intravenous administration of QC immediately after irradiation, lead to decrease of the blood flow only 28 %, and after an hour the blood flow was completely restored. The degree of MCs degranulation after the intravenous administration of HC and QC is almost equal and characterized by a decrease in the number of MCs with complete (anaphylactic) degranulation to 27.5 [21.6; 29.4] and 26.4 [22.5; 32.5] %, respectively, versus 46.9 [47.7; 52] % in the control group (p<0,05); however, after the administration of ES, the results are comparable with the intact control. Non-parametric correlation analysis did not reveale statistically significant difference between blood flow one hour after photodynamic exposure and morphometric types of MCs in groups with various drugs. Conclusion. Differences between the drug effects on the skin blood flow and the IgE-independent MCs activation is confirmed by the absence of a correlation between these parameters. QC, in comparison with ES and HC, is more effective in relation to dysfunction of the skin MCC. Under these conditions, the combined use of anti-inflammatory and antioxidant drugs seems promising.

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