The features of developing rat autoimmune pathology with mitochondrial dysfunction

Abstract

The central role of the mitochondria in energy supply and cell death determines highlight these organelles as one of the promising objects for investigating pathogenesis of immune-mediated inflammatory disorders. The aim: to study features of pathogenesis in rat adjuvant-induced autoimmune pathology separately and in combination with mitochondrial disorders. Materials and methods: Wistar rats were divided into groups of negative control (solvent), positive control (single subcutaneous injection of complete Freund's adjuvant (CAF) at dose of 0.1 ml/200 g body weight), experimental (CAF 0.1 ml/ 200 g body weight and 5 weeks later with cuprizone 0.2% per feed weight). At the end of experiment (7 weeks), animals were tested in the "open field" model, euthanized, and biomaterial was collected to measure the relative mass coefficients of internal organs, hematological and histological studies. We calculated the mean, standard error of the mean; comparison of hypotheses was carried out by paired Student's t-test. Results: in case of impaired immunological tolerance there was detected reduced rat body weight gain during the study period (negative control +74.7 g, positive control +10.3 g) along with modelled mitochondrial dysfunction, a general decrease in weight by 6.7 g was noted. The magnitude of mass coefficients indicate a relative reduction in mass of liver, kidneys, spleen and thymus in experimental animals. The leukocyte counts (x109/L) are as follows: negative control 8.680.37, positive control 10.981.03 (p0.05), experimental group 12.280.63 (p0.001). No significant changes were found in the leukocyte formula and the red cell lineage. During modelled autoimmune pathology, platelet count increased by 22.5% (p0.05), whereas after cuprizone was administered it decreased by 6.3% (relative to the negative control). Mitochondrial dysfunction caused an abrupt decrease in motor activity in rats: the number of crossed sectors in positive control animals was 55.506.91, experimental group 44.503.60 (inter-group comparison, p0.001). Positive control: enlarged lymphatic nodules were found in the spleen, germinal center clarification, wall thickening of the pulpal and central arteries; single foci of hemorrhages in the red pulp. Experimental group: atrophy of lymphoid follicles of varying severity (relative to the groups of negative and positive controls), numerous foci of hemorrhages with hemosiderosis in the red pulp. Conclusion: mitochondrial dysfunction is accompanied by augmented pathogenetic signs of autoimmune pathology, which can serve as one of the keys to understanding the mechanisms of human autoimmunity.

Effect of interferon lambda on the generation of active oxygen species in mice under conditions of oxidative stress induced by Mitomycin C

“…Активные формы кислорода митоходриального происхождения выполняют роль мессенджеров, активируя основной пул иммунокомпетентных клеток, выработку провоспалительных цитокинов, регулируя реакции адаптивного иммунитета (в частности, функции Тлимфоцитов), влияют на течение воспалительной реакции [5,6]. Нарушение процессов СРО и избыточное производство АФК может играть одну из ведущих ролей в этиопатогенезе многих нарушений иммунологической защиты организма [7]. Митомицин С (ММС) является известным препаратом с противоопухолевой, цитотоксической и цитостатической активностью [8].…”