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.

High adjuvant reactogenicity is the main limitation for increasing the effectiveness of vaccine therapy. The aim was to reduce the immunotoxicity effects of complete Freunds adjuvant (CFA) in warm-blooded animals. Materials and methods. The study examined Wistar rats by dividing animals into negative control (solvents); positive control (single subcutaneous CFA injection of 0.1 ml/200 g body weight (b.w.)); the minimum and maximum (per os administration of 1:4 citric and succinic acids in ratio of 17 and 88 mg/kg b.w. during 4 weeks after immunization of CFA) experiment. Body weight, hematological (complete blood count) and biochemical (hydroperoxides, malondialdehyde, catalase activity, mitochondrial dehydrogenase activity) parameters were dynamically investigated. At the end of the experiment, necropsy was performed and the relative internal organ mass coefficients were calculated. The spleen and connective tissue (knee joint) were examined histologically. The median, C25C75 quartiles, MannWhitney U-test were calculated. Results and discussion. it was found that parameters examined were within normal range in animals of negative control group. Immunization of warm-blooded animals with CFA was accompanied by transition of acute-to- chronic inflammatory reaction (week 3 and week 7, respectively). The total leukocyte count increased from 12.5 109 (negative control) up to 26.6 109/L (P = 0.01) on week 3 followed by its decline down to 19.2 109/L (P = 0.01) by week 7. Platelet count also increased significantly: from 506 109 (negative control) up to 656 109/L (P = 0.01, week 3) followed by decrease down to 610 109/L by week 7 (P = 0.01). Activation of lipid peroxidation was manifested by malondialdehyde (MDA) level elevated by 55.861.8% (P = 0.01); the general CFA-related toxic effect resulted in 11.7% weight loss (P = 0.01), spleen swelling and thymus reduction. Administration of antioxidant acids led to a dose-dependent decline in inflammation (leukocyte count at the minimum dosage 19.6 10920.9 109/L; at the maximum 16.6 10916.0 109/L), as well as normalized the platelet/leukocyte index up to 29.536.3 (positive control 24.6, negative control 40.5). The acid-related protective effect was also manifested as maintained body weight, activated catalase and inhibited lipid peroxidation. The therapeutic effect in alleviated degenerative changes in the spleen and connective tissue were revealed: reduced hemorrhagic focuses and swelling as well as preserved histoarchitectonics. Conclusion. The use of citric and succinic acids contributes to profoundly lowered CFA toxicity due to increased total antioxidant status, inhibited lipid peroxidation, improved mitochondrial metabolic activity, which ultimately lead to a decline in general systemic inflammation and allows to recommend such acids as immunoprotectors from oil adjuvant-coupled effects.

The aim is to study the combined effects of heavy metals and antibiotics on the genetic cell apparatus, to assess the possibility of correction of the genotoxic effect of the immunomodulator. Using Ford-Hamerton method the cytogenetic effects of the antibiotic Ceftriaxone (450 mg / kg) on the background of cadmium chloride (1 х 10-3M), lead acetate (1 х 10-3 M) and imunofan (0.004 mg/kg) were estimated on marrow cells of 102 male rats of Wistar population. Results. Imunofan showed antimutagenic effect: the number of chromosomal aberrations compared with the negative control (1.5 ± 0.50) % decreased 3 times (0.50 ± 0.29) %; the genome protection coefficient (Fp) was 66.67 %. The expression coefficient of the mutagenic effect of Cd (II) is 3.5 units, the number of chromosomal aberrations - (5.3 ± 0.91)%; the expression coefficient of the mutagenic effect Pb (II) was 3 units; the number of chromosomal aberrations - (4.5 ± 0.85) %; p < 0.001. Ceftriaxone in the maximum therapeutic dose had mild mutagenic properties: the expression coefficient of the mutagenic effect -2.2 units; the number of chromosomal aberrations (3.3 ± 0.73) %. In the variants [Pb (II) + ceftriaxone] and [Cd (II) + ceftriaxone], the mutagenic effect increased in comparison with the mono-effect of substances: the expression coefficient of the mutagenic effect, respectively 3.9 and 4.1 units; the number of chromosomal aberrations - (5.86 ± 0.95) %; p

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Вовлеченность широких слоев населения (от 5 до 10%) в патологию аутоиммунных заболеваний, включающих в себя более 100 нозологических форм, определяет актуальность поиска эффективных и безопасных методов коррекции клинических признаков нарушений здоровья населения. Целью работы являлось изучение эффективности коррекции патологических нарушений смесью лимонной и янтарной кислот в модели адъювантного аутоиммунного ревматоидного артрита у крыс. Согласно полученным результатам, позитивный эффект от применения смеси лимонной и янтарной кислот обеспечивается контролируемым увеличением процессов перекисного окисления липидов, способствующих выработке компонентов гуморального иммунитета, активацией ферментного звена антиоксидантной защиты, снижением дегенеративных изменений в суставном аппарате и, как следствие, увеличением двигательной активности животных. Достоверное увеличение содержания в крови леченых животных гидроперекисей на 13% (относительно группы с модельной патологией) скомпенсировано ростом каталазы на 7% (p<0,01), что служит позитивным диагностическим признаком. На фоне коррекции смесью органических кислот у подопытных животных снижалась отечность в синовиальной оболочке, сохранялась гистоархитектоника надхрящницы, гиалинового хряща и субхондральной кости. Позитивные изменения выражались также в виде дозозависимой нормализации поведенческих (актометрических) реакций в модели «открытое поле» -на 30-40% (p<0,05 относительно группы с модельной патологией). Включение доступных, действенных и безопасных антиоксидантов в схемы профилактики и лечения может способствовать значительному улучшению эффективности терапии аутоиммунных заболеваний, и в частности ревматоидного артрита (РА). Ключевые слова: адъювант Фрейнда, адъювантная терапия, аутоиммунный ревматоидный артрит, лимфоциты, митохондрии, профилактика ревматоидного артрита, сукцинатдегидрогеназа.