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.

Изучалось влияние двухнедельного приёма гидрокарбонатной углекисло-хлоридно-натриевой минеральной воды Северной Осетии «Хилак» с общей минерализацией 2,1-2,3 г/л и повышенным содержанием железа, бора и кремния на морфофункциональное состояние печени крыс линии Вистар с токсическим гепатитом, смоделированным путем трёхкратного внутрижелудочного введения тетрахлорметана в дозе 1,5 мл/кг, разведенного равным количеством оливкового масла. Спустя три дня после введения смеси морфологически в печени отмечалось полнокровие вен, расширение синусоидов, набухание и гиалиново-капельная дистрофия гепатоцитов, а функционально в крови выявлялось усиление пероксидации липидов (повышение содержания гидроперекисей и малонового диальдегида) и ослабление антиоксидантной защиты (снижение активности каталазы и супероксиддисмутазы), повышение содержания билирубина, активности щелочной фосфатазы и аланинаминотранферазы, и одновременное снижение содержания холестерина, гемоглобина, количества эритроцитов, гематокритного числа и коэффициента де Ритиса. Выявленные изменение сохранялись, если крысам в течение двух недель давать водопроводную воду, в то время как приём минеральной воды в свободном режиме оказывал нормализующее влияние на исследуемые показатели, что позволяет, после проведения дальнейших исследований, рекомендовать больным с токсической патологией печени приём данной минеральной воды в качестве лечебного средства. Ключевые слова: тетрахлорметан, токсический гепатит, минеральная вода, пероксидация липидов, антиоксидантная система, щелочная фосфатаза, трансферазы, холестерин, билирубин, эритроциты, гемоглобин.

Выяснялась чувствительность нефрона к антидиуретическому гормону у крыс с моделью почечной недостаточности. Исследования проводили на 78-и крысах линии Вистар (28 интактных и 50 с почечной недостаточностью, создаваемой в/м введением глицерина в дозе 0,8 мл/100г, и с повторным введением через две недели и один месяц). Антидиуретический гормон, в виде десмопрессина, вводили в/м в дозе 1,5 мкг/кг на фоне 5,0 % от веса крыс водной нагрузки водопроводной водой. Десмопрессин у 75,0 % контрольных крыс в течение первого часа вызвал отсутствие мочи, а у оставшихся 25,0 % -трехкратное её уменьшение. Сниженным диурез был и за второй час. Отмеченные изменения были обусловлены усилением канальцевой реабсорбции воды. Введение десмопрессина крысам с почечной недостаточностью в олигоанурическую фазу (через две недели) оказывает усиленное антидиуретическое действие, полностью блокируя водный диурез не только в первый час, но и за второй. На высоте полиурической фазы почечной недостаточности (через 1 месяц) эффект десмопрессина проявляется слабее, хотя канальцевая реабсорбция остается усиленной, но одновременно ускоряется и клубочковая фильтрация, а через три месяца (хроническая фаза) введение десмопрессина практически перестает оказывать характерное антидиуретическое действие. Ключевые слова: почечная недостаточность, десмопрессин, водовыделительная функция, канальцевая реабсорбция. The sensitivity of the nephron to antidiuretic hormone in rats with a model of renal failure was elucidated. The studies were carried out on 78 Wistar rats (28 intact and 50 with renal insufficiency, created intramuscularly by the administration of glycerin at a dose of 0.8 ml/100 g, with repeated administration in two weeks and one month). Antidiuretic hormone, in the form of desmopressin, was administered intramuscularly at a dose of 1.5 μg/kg against a background of 5.0 % of the weight of the rats of the water load with tap water. Desmopressin in 75.0 % of the control rats during the first hour caused no urine, while the remaining 25.0 % caused a three-fold decrease. Decreased diuresis was in the second hour. The changes noted were due to increased tubular water reabsorption. The administration of desmopressin to rats with renal insufficiency in the oligoanuric phase (after two weeks) exerts an enhanced antidiuretic effect, completely blocking diuresis not only in the first hour after the water load, but also in the second. At the height of the polyuric phase of renal failure (after 1 month), the effect of desmopressin is less pronounced, although tubular reabsorption is enhanced, but glomerular filtration is also intensified, and after three months (chronic phase) it practically ceases to have a characteristic antidiuretic effect.Постоянное повышение частоты заболеваний, их омоложение, более сложные формы проявлений, среди которых болезни почек занимают значительное место как у нас в стране, так и повсеместно, требует поиска не только новых методов лечения, диагностики, но и выяснения механизмов, лежащих в основе этих заболеваний, что, несомненно,...

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